Ntsuam xyuas. Nruab nrab tswj ntawm rab qau erection: Ib tug rov xyuas ntawm lub luag hauj lwm ntawm oxytocin thiab nws cov nrog dopamine thiab glutamic acid hauv txiv neej nas (2011)

Neurosci Biobehav Rev. 2011 Jan; 35 (3): 939-55. doi: 10.1016 / j.neubiorev.2010.10.014. Epub 2010 Nov 2.

Melis MR¹, Argiolas A.

¹Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, CA, Ltalis. [email tiv thaiv]

HLWV

Oxytocin yog ib qho muaj zog ntawm cov pob txha rab qau thaum txhaj tshuaj mus rau hauv lub hauv nruab siab. Nyob rau hauv cov txiv neej nas, feem ntau lub hlwb lub hlwb rau cov nyhuv pro-erectile ntawm oxytocin yog paraventricular nucleus ntawm cov hypothalamus. Qhov cov keeb thiab cov cheeb tsam puag ncig muaj cov kab mob ntawm lub cev ntawm txhua oxytocinergic neurons projecting rau qhov chaw hypothalamic hlwb thiab cov leeg nrob qaum. Qhov kev ntsuam xyuas no qhia tias oxytocin induces penile erection kuj thaum txhaj hauv qee qhov chaw no (xws li, ventral tegmental, ventral subiculum ntawm hippocampus, posteromedial cortical nucleus ntawm amygdala thiab thoraco-lumbar spinal cord). Microinjection kev tshawb fawb nrog intra-cerebral microdialysis thiab ob chav immunofluorescence cov kev tshawb fawb pom tias oxytocin nyob rau hauv cov chaw activates ncaj qha los yog indirectly (mas los ntawm cov kua qaub glutamic) mesolimbic dopaminergic neurons. Dopamine uas tau tso tawm rau hauv cov keeb kwm nucleus nyob rau hauv lem activates neural txoj hau kev ua rau kev ua ntawm incerto-hypothalamic dopaminergic neurons nyob rau hauv paraventricular nucleus. Qhov no tsuas tsis yog oxytocinergic neurons projecting rau tus txha nqaj qaum thiab kev kho nruab nrab cov pob qij txha, tab sis kuj yog cov neeg ua haujlwm rau qhov chaw siab tshaj qhov chaw hypothalamic, modulating ncaj qha los yog tsis ncaj (los ntawm glutamic acid) kev ua ntawm mesolimbic dopaminergic neurons tswj motivation thiab nqi zog. Ua ke cov dej neural no yuav yog ib txoj kev ntsuas hypothetical, uas yog lub luag hauj lwm tsis yog nyob hauv theem ntawm kev ua haujlwm ntawm kev sib deev (erectile muaj nuj nqi thiab kev sib txuas tes), tiam sis tseem muaj cov kev txhawb zog thiab kev muaj txiaj ntsim ntawm lub sij hawm npaj ntawm kev coj tus cwj pwm.

1.Introduction

Penile erection yog ib tug txiv neej kev sib deev uas plays lub luag hauj lwm tseem ceeb hauv kev yug me nyuam ntawm cov txiv neej nrog rau tus txiv neej, thiab qhov ntawd kuj tseem tau pom hauv cov ntsiab lus sib txawv los ntawm cov neeg ncaj qha txog kev tu tub tu kiv. Raws li cov ntsiab lus hauv kev siv rab qau erection tshwm sim, ntau lub hauv paus thiab peripheral neural thiab / los yog humoral mechanisms koom nrog nws cov kev cai (saib Meisel thiab Sachs, 1994; Argiolas thiab Melis, 1995, 2004, 2005; Sachs, 2000, 2007; McKenna, 2000; Giuliano thiab Rampin, 2000, 2004; Andersson, 2001; Melis thiab Argiolas, 1995a, 2003; Hull et al., 2002). Cov central neurotransmitters thiab neuropeptides uas tswj kev siv tshuaj tiv thaiv penile, qhov zoo tshaj plaws paub yog dopamine, serotonin, excitatory amino acids, nitric oxide, adrenocorticotropin, oxytocin thiab opioid peptides. Lawv tuaj yeem pab txhawb los yog tsis ua rau cov pob txha txhav siv los ntawm kev ua rau hauv ntau qhov chaw hauv hlwb, piv txwv li, thaj chaw nruab nrab, qhov chaw muaj zog ntawm hypothalamus, lub ventral tegmental, hippocampus, lub amygdala, lub txaj nucleus ntawm lub davhlau ya nyob twg, lub nucleus accumbens, medulla oblongata thiab cov leeg nrob qaum (Saib 1) (saib Meisel thiab Sachs, 1994; Witt thiab Insel, 1994; Stancampiano thiab Lwm Yam, 1994; Argiolas thiab Melis, 1995, 2005; Argiolas, 1999; Bancila et al., 2002; Giuliano thiab Rampin, 2000, McKenna, 2000; Andersson, 2001; Hull li al, 2002; Coolen et al., 2004).

Oxytocin, neurohypophyseal peptide zoo paub rau nws lub luag hauj lwm hormonal hauv lactation thiab parturition, yog tam sim no nyob rau cov pojniam thiab cov txiv neej, tsis yog hauv cov leeg lub cev nrog lub cev ntawm lub cev nyob rau hauv cov quag thiab supraoptic nuclei ntawm hypothalamus projecting rau cov neurohypophysis, tab sis kuj nyob rau hauv neurons projecting los ntawm paraventricular nucleus thiab ib puag ncig cov qauv rau extrahypothalamic hlwb thaj chaw (ie, septum, ventral tegmental, hippocampus, amygdala, medulla oblongata thiab cov leeg nrob qaum). Cov neurons no xav tias muaj kev koom tes hauv ntau lub hauv paus ua haujlwm, xws li kev nco, kev kawm, kev coj tus cwj pwm thiab kev coj tus cwj pwm, nrog rau kev siv tshuaj (penile erection and copulatory behavior) (saib Buijs, 1978; Sofroniew, 1983; Argiolas thiab Gessa, 1991; , 1992; Carter, 1992; Wagner thiab Clemens, 1993; Ivell thiab Russell, 1995; Carter thiab lwm tus, 1997; Tang thiab al., 1998; Veronneau-Longueville et al., 1999). Qhov tseeb, oxytocin tswj kev ua haujlwm thiab cov txiv neej pw hauv cov nas, nas, luav thiab liab (saib Argiolas thiab Gessa, 1991; Carter, 1992; Pedersen et al., 1992; Argiolas thiab Melis, 1995, 2004; Argiolas, 1999). Qhov no kuj tshwm sim hauv tib neeg, vim ntshav oxytocin yog nce los ntawm kev sib deev stimuli, tshwj xeeb tshaj yog thaum ejaculation (Carmichael thiab al., 1987; Murphy li al., 1987) thiab los ntawm kev tswj ntawm lub mis thiab ntawm genitalia, uas feem ntau tshwm sim thaum sib deev intercourse (Tindall, 1974).

Ib qho yooj yim ntawm oxytocin rau cov txiv neej muaj kev sib deev yog thawj zaug tau pom los ntawm kev muaj peev xwm ntawm cov hlab ntsha oxytocin los txo cov latency mus rau tus thawj ejaculation thiab retard kev sib deev ntawm txiv neej rabbits paired nrog receptive pojniam (Melin thiab Kihlstrom, 1963). Txawm li cas los xij, qhov teebmeem ntawm kev sib deev ntawm oxytocin tau raug lees paub tias tsuas yog nyob rau hauv eighties xwb. Oxytocin muab rau hauv nruab nrab ntawm cov khoom nanogram hauv ces tau pom muaj qhov qoob loo (erosion) (Argiolas et al., 1985, 1986) thiab kom muaj kev txhim kho tus cwj pwm (Arletti et al., 1985) hauv cov txiv neej nas, thiab nce lordosis hauv pojniam cov niam (Arletti thiab Bertolini, 1985; Caldwell et al., 1986), thaj yeeb los ntawm kev ua rau lub cev tsis haum rau oxytocinergic receptors (saib Argiolas thiab Melis, 1995, 2004; Argiolas, 1999; Melis thiab Argiolas, 2003; Oxytocin pab kho tus cwj pwm tsis zoo hauv kev sib deev (Arletti li al., 1985), tiam sis tseem nyob rau hauv cov laus txiv neej (Arletti li al., 1990), thiab nyob rau hauv tseem ceeb, tab sis tsis nyob rau hauv subordinate, txiv neej squirrel liab (Winslow thiab Insel , 1991).

Cov nyhuv pro-erectile ntawm oxytocin yog testosterone-dependent, vim nws yog abolished los ntawm hypophysectomy thiab castration, thiab rov los ntawm supplementation nrog testosterone los yog nws cov metabolites, estradiol thiab 5_-dihydro-testosterone muab ua ke (Melis li al., 1994a). Qhov chaw siab tshaj plaws rau lub hlwb rau qhov kev qaug zog ntawm cov hlab ntshav ntawm oxytocin yog qhov paraventricular nucleus ntawm hypothalamus (Melis thiab lwm tus, 1986), uas tag nrho cov kev kuaj ntxiv ntawm cov hypothalamic oxytocinergic originates (saib saum toj no). Ntawm no, oxytocin tau pom tias yuav ua rau qaug zog rab yaj yig erection (thiab yawning) thaum txhaj tshuaj ntau npaum li 3 pmol (saib Tshooj 2.1 hauv qab). Oxytocin vim khomob raug ua rau thaum lub sij hawm txhaj koob tshuaj tiv thaiv rau hauv hippocampus CA1, tab sis tsis yog nyob rau ntawm lub plab hnyuv qis (saib Tshooj 2.3 hauv qab), qhov tom qab septum, qhov caudate nucleus, thaj chaw nruab nrab ntawm thaj tsam, lub ventromedial nucleus ntawm hypothalamus supraoptic nucleus (Melis li al., 1986). Raws li lub mechanism uas oxytocin ua nyob rau hauv paraventricular nucleus los induce no kev sib deev teb, ntau cov kev tshawb fawb qhia tias oxytocin activates nws tus kheej neurons. Nyob rau hauv txoj kab no, kev sib deev kev sib txuas ua rau FOS, cov khoom noob ntawm cov tsiaj txhu tam sim thaum ntxov hauv cov kabmob ntawm cov hlab ntsha ntawm cov hlab ntsha, uas yog kev koom tes hauv kev tswj ntawm rab qau erection (saib Witt thiab Insel, 1994 thiab cov references nyob rau hauv cov poj niam uas tsis muaj peev xwm (piv txwv li, qhov tsis muaj peev xwm ntawm ib tug neeg laus txiv neej tus txiv neej mus nrog tus poj niam tus poj niam-progesteroneprimed receptive) al., 1997).

Txawm hais tias muaj oxytocin cuam tshuam txog cov theem ntawm lub sijhawm lossis qhov theem ntawm kev sib deev ntawm kev sib deev tsis paub meej tam sim no. Raws li oxytocin induces penile erection thiab cov nyhuv loj ntawm oxytocin rau tus cwj pwm copulatory yog txo tus tom qab ejaculatory interval hauv txiv neej (Arletti li al., 1985), nws tsim nyog los xav tias tus peptide pab txoj kev sib deev. Txawm li cas los xij, oxytocin kuj tseem tuaj yeem ua rau muaj kev sib txuam nrog kev sib deev (saib Pedersen li al., 1992; Carter et al., 1997; Ivell thiab Russel, 1995), thiab oxytocin reseptor antagonists tiv thaiv tsis tau cov tshuaj (Melis li al., 1999a), uas (saib Sachs, 1997, 2000, 2007; Melis et al., 1998, 1999b thiab cov neeg ua tim khawv nyob rau ntawd), kev muaj peev xwm ntawm oxytocin nyob rau hauv kev sib deev arousal thiab kev sib deev motivation tsis tau txiav txim.

Cov kev rov ntsuam xyuas no piav qhia tawm thiab luam tawm tsis tau cov kev tshawb fawb tsis ntev los no, uas qhia tau tias oxytocin induces penile erection tsis tsuas yog thaum txhaj rau hauv paraventricular nucleus ntawm cov hypothalamus, tab sis kuj nyob lwm qhov ntxiv hypothalamic hlwb chaw, xws li ventral tegmental tsam (Melis li al., 2007, 2009a; Succu li al., 2008), tnws ventral subiculum ntawm hippocampus thiab posterior posterior nucleus ntawm amygdala (Melis li al., 2009b, 2010), uas yog cov tseem ceeb ntawm cov kev limbic thiab xav tau los ua si lub luag haujlwm tseem ceeb hauv kev txhawb siab thiab kev sib tw. Cov kev tshawb fawb no qhia tias oxytocin koom rau hauv neural circuits, uas muaj lwm cov neurotransmitters, xws li dopamine thiab glutamic acid, thiab lwm qhov chaw hauv lub hlwb uas tsis yog qhov paraventricular nucleus, xws li, ventral tegmental, nucleus accumbens, hippocampus thiab cheeb tsam tsis tau txheeb xyuas. Cov circuits muaj feem yuav ua rau kev sib haum xeeb ntawm mesolimbic thiab incerto-hypothalamic dopaminergic system, thiab los ua si lub luag hauj lwm tsis yog nyob hauv theem ntawm cov poj niam txiv neej tus cwj pwm (xws li, erection erection thiab copulation), tab sis kuj muaj kev sib deev kev xav thiab kev sib deev arousal, yog li muab lub neural substrate rau dab lub motivational thiab nqi zog ntawm kev sib deev ua si.

2. Oxytocin influences penile erection los ntawm kev ua nyob hauv cov cheeb tsam hauv lub hlwb txawv

2.1. Lub paraventricular nucleus ntawm hypothalamus

Raws li tau hais los saum toj qhov paraventricular nucleus ntawm cov hypothalamus tau sai sai raws li lub paj hlwb feem ntau rhiab rau cov nyhuv pro-erectile ntawm oxytocin. Thaum txhaj tshuaj tiv thaiv ntawm cov keeb kwm no, oxytocin twb pom muaj nyob rau hauv tsawg li 3 ng (3 pmol) (Melis li al., 1986). Cov kev tshawb nrhiav ntawm kev ua haujlwm ntawm kev ua haujlwm - qhia tias oxytocin huas penile erection mediated los ntawm uterinetype oxytocin receptors, koom nrog Ca2 + influx mus rau hauv lub cev ntawm oxytocinergic neurons projecting rau hypothalamic hlwb qhov chaw thiab rau activation ntawm nitric oxide-synthase. Nitric oxide nyeg los ntawm kev ua ib tus tub xa xov xwm nrog ib tus neeg tseem tsis paub txog (tsis muaj guanylate cyclase) ua rau kev ua rau ntawm oxytocinergic neurons projecting rau tus txha caj qaum thiab ntxiv qhov hypothalamic hlwb chaw, inducing penile erection (daim duab 1) (saib hauv qab thiab Argiolas thiab Melis, 1995, 2004, 2005 thiab cov neeg ua tim khawv nyob hauv). Lub peev xwm ntawm oxytocin mus qhib nws tus kheej neurons

Daim duab 1. (MISSING) Cov sawv cev ntawm oxytocinergic neurons, uas tsim tawm hauv qhov chaw parguentricular ntawm hypothalamus thiab qhov project rau hypothalamic hlwb chaw, xws li cov leeg txha caj qaum, VTA, hippocampus, amygdala, thiab lwm yam. Qhov ua kom cov neurons no los ntawm dopamine, excitatory amino acids, oxytocin nws tus kheej, hexarelin analogue peptides thiab VGF-derived peptides ua rau rab qau erection, uas yuav raug txo thiab / los yog abolished los ntawm stimulation GABAergic, opioid thiab cannabinoid CB1 receptors. Kev qhib rau ntawm oxytocinergic neurons yog qhov ua rau kev ua rau cov nitric oxide-synthase tam sim no nyob rau hauv cov neurons. Qhov tseeb yog cov tshuaj nitrogen oxide tsim los ntawm cov stimulation ntawm dopamine, excitatory amino acid lossis oxytocin receptors los yog exogenous nitric oxide, uas muab tau los ntawm nitric oxide hloov tau ncaj qha mus rau hauv paraventricular nucleus, activates oxytocinergic neurons los ntawm ib qho tsis tau muaj tseeb mechanism, thaj tsis txheeb tus stimulation ntawm guanylate cyclase. Qhov no ua rau muaj kev tso tawm ntawm oxytocin nyob rau hauv cov leeg txha caj qaum thiab hauv qhov chaw ntxiv hypothalamic hlwb. Qee cov ntsiab lus ntawm cov mechanisms uas oxytocin induces penile erection thaum tso tawm hauv cov cheeb tsam no, xws li, VTA, lub ventral subiculum thiab cov amygdala raug piav nyob rau hauv cov cheeb tsam ntawm lub hlwb hauv cheeb tsam. Ntawm no, oxytocin ua rau nws tus kheej receptors thiab tsub kom tsis muaj ntau lawm, uas ua rau rab qau erection li pom hauv lub PVN. Txawm li cas los, ntawm variance nrog lub PVN, nyob rau hauv cov caudal VTA tsis activates guanylate cyclase. Qhov no ua rau kev nce hauv cGMP concentration ua rau cov activation ntawm mesolimbic dopaminergic neurons thiab rab qau erection. Hauv VS TSIS no qhib cov txheej txheem glutamatergic neurons rau cov cheeb tsam nrawm ntxiv, nrog rau VTA. Glutamic acid nyob rau hauv VTA activates tig mesolimbic dopaminergic neurons raws li pom muaj oxytocin. Mechanisms zoo ib yam li cov neeg tau hais los saum no kuj yuav khiav lag luam thaum muaj roj ntsha tshwm sim hauv kev siv dag zog, uas yog thaum cov txiv neej nas tso rau hauv cov poj niam uas tsis tuaj yeem tso tau (xws li, tsis muaj leej twg) los yog thaum lub sij hawm luam.

nyob hauv txoj kev sib tw paraventricular tau txais kev txhawb los ntawm kev tshawb fawb qhia tias: (1) oxytocin receptors yog tam sim no nyob rau hauv cov ntsiab lus ntawm qhov hypothalamic nucleus (Freund-Mercier li al., 1987; Freund-Mercier thiab Stoeckel, 1995); (2) oxytocin facilitates nws tso tawm hauv vitro thiab vivo (Freund-Mercier thiab Richard, 1981, 1984; Moos thiab lwm tus, 1984); thiab (3) oxytocin excites nws tus kheej neurons los ntawm cov ua yeeb yam hauv cov keeb kwm paraventricular (Yamashita li al., 1987). Tshaj li, oxytocinergic synapses impinging ntawm lub cev ntawm lub cev ntawm magnocellular oxytocinergic neurons kuj tau pom nyob rau hauv lub paraventricular thiab supraoptic nucleus ntawm hypothalamus (Theodosis, 1985). Thaum kawg, rhuav tshem ntawm central oxytocinergic neurons los ntawm electrolytic los yog tshuaj lom neeg excitotoxic lesions ntawm paraventricular nucleus, uas tag nrho oxytocin cov ntsiab lus thoob plaws hauv nruab nrab lub paj hlwb thiab tus txha caj qaum, tshem tawm tsis tau tsuas yog pro-erectile nyhav ntawm oxytocin, tab sis kuj impairs yeeb tshuaj-vim penile erection thiab tsis muaj kev sib txuas lus (saib hauv qab thiab Argiolas li al., 1987a, b; Liu et al., 1997 thiab cov neeg ua tim khawv nyob hauv). Cov qhabnias zoo sib xws rau cov neeg uas pom muaj qhov teebmeem ntawm qhov paraventricular nucleus tau pom muaj zog thiab xaiv cov oxytocin receptor antagonists. Muaj tseeb tiag, cov sib txuas ntawm cov nucleus hauv qhov nanemos no tau tiv thaiv tag nrho cov kev siv zes qe menyuam, thaum lub sij hawm thaum muab rau hauv lub plhaub zuj zus tiv thaiv tsis tau tsuas yog siv tshuaj tiv thaiv (penile erections) los ntawm oxytocin xwb, tab sis kuj tseem siv tshuaj xoo hluav taws xob (saib 3 nram qab no thiab Argiolas thiab Melis, 1995, 2004, 2005 thiab cov neeg ua tim khawv nyob rau ntawd) thiab tsis muaj kev sib txuas lus (Melis thiab lwm tus, 1999a), thiab tau zoo heev rau kev puas tsuaj tus cwj pwm ntawm cov poj niam txiv neej (Argiolas et al., 1988). Tsis tas li ntawd, kev sib deev kev sib cuam tshuam FOS, tus noob khoom ntawm tus poj niam thaum ntxov c-fos nyob rau hauv paraventricular oxytocinergic neurons projecting rau tus txha caj qaum kev koom tes hauv kev tswj ntawm rab qaum erection (saib Witt thiab Insel, 1994 thiab cov lus nug nyob hauv). Thaum kawg, kev sib deev impotence (piv txwv li, qhov tsis muaj peev xwm ntawm ib tug neeg laus txiv neej tus txiv neej mus nrog ib tus poj niam uas yog cov poj niam uas ua rau tus poj niam hla (progesteroneprimed receptive receptive female) hraws li kuj tau txuam rau hauv tus txiv neej nas nrog tsawg theem ntawm oxytocin mRNA thiab ntawm nitric-oxide synthase nyob rau hauv paraventricular nucleus ntawm hypothalamus (Benelli et al., 1995; Arletti et al., 1997) (rau cov kev tshawb fawb txog kev sib tham saib Argiolas, 1999; Argiolas thiab Melis, 2004, 2005).

2.2. Lub ventral tegmental cheeb tsam

Lub ventral tegmental thaj tsam tau pom xwb tsis ntev los no raws li lub paj hlwb ntawm qhov chaw oxytocin induces penile erection. Qhov chaw no muaj oxytocinergic hlab ntsha kawg tawm hauv cov kabmob paragentricular nucleus thiab oxytocin receptors (Freund-Mercier li al., 1987; Vaccari et al., 1998). Ntau dua li precisely, oxytocin tau pom muaj peev xwm ntawm kuvnducing penile erection thaum txhaj tshuaj tua kab mob mus rau hauv caudal, tab sis tsis nyob rau hauv cheeb tsam ventral tegmental nyob hauv ib hom tshuaj (raws li Melis li al., 2007). Cov nquag siv zog tau siab tshaj cov uas xav tau thaum uas txhaj rau hauv cov leeg parabentricular nucleus thiab zoo ib yam li cov uas ua rau cov pob txha rab qau thaum txhaj rau hauv ventral subiculum ntawm hippocampus los yog hauv posteromedial cortical nucleus ntawm amygdala (saib hauv qab). Thaj tsam, cov nyhuv pro-erectile kho tau los ntawm kev ua kom cov mesolimbic dopaminergic neurons projecting rau lub plhaub ntawm cov nucleus accumbens, uas nyeg activates tsis tau paub txog neural txoj kev projecting rau incerto-hypothalamic dopaminergic neurons impinging rau paraventricular oxytocinergic neurons mediating penile erection (Melis li al., 2007, 2009a).

Raws li cov mechanism uas oxytocin activates dopaminergic neurotransmission hauv cheeb tsam ventral tegmental, cov ntaub ntawv qhia tau hais tias oxytocin stimulates oxytocinergic receptors nyob hauv lub cev ntawm mesolimbic dopaminergic neurons. Qhov no yuav ua rau Ca2 + kev tawm hauv lub cev ntawm lub cev ntawm dopaminergic neurons, yog li ua kom muaj nitrric oxide-synthase (Succu li al., 2008). Ntawm qhov txawv txav nrog paraventricular nucleus (saib Tshooj 3 hauv qab), nitric oxide nyeg qhib guanylate cyclase, li no nce lub concentration ntawm cyclic GMP. Nyob rau hauv txoj kab nrog txoj kev no, xws li d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, muaj zog oxytocin antagonist, los yog S-methyl-thio-l-citrulline, lub hwj chim inhibitor ntawm neuronal nitric oxide-synthase, caudal ventral tegmental thaj av ua ntej oxytocin, abolished penile erection thiab kev nce rau ntxiv-cellular dopamine concentration nyob rau hauv lub plhaub ntawm lub nucleus accumbens induced by oxytocin. Ntxiv mus, 8-bromo-cyclic GMP, ib qho active phosphodiesterase-resistant cyclic GMP analogue, induces penile erection thaum txhaj rau hauv caudal ventral tegmental tsam thiab tsub kom ntxiv-cellular dopamine concentration hauv lub plhaub ntawm nucleus accumbens, raws li pom muaj oxytocin txhaj rau hauv qhov caudal ventral tegmental (Succu li al., 2008; Melis et al., 2009a) (saib daim duab 2).

Txhua zaus nyob rau hauv txoj kab no mechanism, haloperidol, hwj chim dopamine D2 receptor antagonist, txhaj rau hauv lub plhaub ntawm cov keeb kwm nucleus reduces penile erection induced by oxytocin txhaj rau hauv ventral tegmental cheeb tsam (Melis li al., 2007). Cov txheej txheem saum toj no kuj tau kev txhawb los ntawm kev tshawb fawb kab mob dual immuno-fluorescence, uas qhia tias oxytocin fibers impinge rau ntawm lub cev ntawm dopaminergic neurons hauv cov caudal ventral tegmental, uas tau yav tas los sau nrog retrograde tracer Fluorogold txhaj rau hauv lub plhaub ntawm cov keeb kwm nucleus ( Melis li al., 2007; Succu li al., 2008). Cov activations ntawm cov dopaminergic neurons thiab cov dopamine receptors nyob rau hauv lub nucleus accumbens txhuas kom dhau mus ua kom cov neural txoj kev tsis tau qhia, uas stimulate incerto-hypothalamic dopaminergic neurons tso dopamine nyob rau hauv paraventricular nucleus, ua li no activating oxytocinergic neurons projecting rau cov tus txha nqaj qaum thiab kev sib hais kom sib phim erection (saib saum toj no thiab Melis li al., 2007; Succu li al., 2007, 2008). Xwb, oxytocin txhaj rau hauv caudal ventral tegmental ntawm ib koob uas ua rau cov pob txha penile erection, ntau ntxiv-cellular dopamine concentration hauv dialysate tau tsuas yog los ntawm cov nucleus accumbens, tab sis kuj los ntawm paraventricular nucleus (Succu li al., 2007).

2.3. Lub hippocampus

CA1 teb ntawm hippocampus yog lwm qhov paj hlwb nyob hauv cov oxytocinergic fibers thiab cov kws kho mob pom tau los ntawm cov kev tshawb fawb dhau los uas qhov kev txhaj tshuaj ntawm oxytocin vim khaus penile erection (saib Bujis, 1978; Sofroniew, 1983). Txawm li cas los xij, thaum muaj qhov sib txawv ntawm qhov chaw parabentricular nucleus, nov oxytocin no muaj peev xwm ua rau inducing penile erection thaum txhaj koob tshuaj tiv thaiv nkaus xwb thiab txhaj tshuaj ntau dua li cov uas pom muaj nyob hauv paraventricular nucleus (Melis li al., 1986; Chen et al., 1992). Kev siv oxytocin mus rau hauv subiculum tau pom cov neeg tsis tuaj yeem ua cov kev tshawb fawb ua ntej. Txawm li cas los xij, cov kev tshawb fawb tsis ntev los no thiab ntau yam kev tshawb fawb ua rau muaj kev qhia txog tus kheej thaj tsam ntawm ventral subiculum nyob rau hauv uas txhaj cov oxytocin muaj peev xwm ntawm inducing penile erection nyob rau hauv ib koob-raws li hais (Melis li al., 2009b). Txoj kev nyhav ntawm oxytocin uas tau txhaj rau hauv thaj chaw ntawm lub hlwb tau pom zoo nyob rau hauv cov tshuaj tiv thaiv kab mob hauv cov ventral tegmental tom qab txhaj tshuaj tom qab unilateral (Melis li al., 2007), raws li muaj nyob rau hauv qhov chaw paraventricular nucleus. Thaj, oxytocin txhaj rau hauv ventral subiculum induces penile erection los ntawm activating oxytocinergic receptors nyob rau hauv neurons muaj nitric oxide-synthase, yuav ua rau tus nce hauv nitric oxide ntau lawm. Nitric oxide nyeg los ntawm kev sib txuas lus ua tub txib intercellular pib ua glutamic acid neurotransmission, ua rau cov pob txha rab yaj ntxig, tejzaum nws los ntawm neural (glutamatergic) efferent projections los ntawm ventral subiculum mus rau lwm qhov chaw hippocampal hlwb modulating cov kev ua ntawm mesolimbic dopaminergic neurons (xws li, ventral tegmental, prefrontal cortex, paraventricular nucleus) (saib hauv qab thiab Melis, 2007, 2009b; Succu et al., 2008).

Lub tswv yim ntawm qhov kev txiav txim no yog txhawb los ntawm cov kev kuaj mob intra-cerebral microdialysis, uas qhia tias oxytocin txhaj rau hauv ventral subiculum nyob rau hauv koob tshuaj uas ua rau plab hnyuv erection, nce qib nitric oxide ntau lawm thiab extracellular glutamic acid concentration hauv dialysate los ntawm ventral subiculum (Melis et al. , 2010) thiab ntawm extracellular dopamine nyob rau hauv lub nucleus accumbens (Melis li al., 2007). Cov lus teb no yog antagonized tsis tsuas yog los ntawm oxytocin receptor antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, tab sis kuj los ntawm neuronal nitric oxide-synthase inhibitor S-methyl-thio-lcitrulline thiab los ntawm nitric oxide scavenger hemoglobin muab rau hauv ventral subiculum ob peb feeb ua ntej oxytocin (Melis li al., 2010).

Ntxiv mus, nyob rau hauv txoj kab no nrog kev txiav txim siab, kev ua rau glutamatergic neurotransmission los ntawm NMDA txhaj rau hauv ventral subiculum induces penile erection (Melis li al., 2010). Lub phenotype ntawm efferent projections los ntawm ventral subiculum, uas ua rau lub activation ntawm mesolimbic dopaminergic neurons thiab nce ntawm ntxiv-cellular dopamine nyob rau hauv lub nucleus accumbens, yog tam sim no tsis paub. Txawm li cas los xij, vim tias kev siv tshuaj tiv thaiv kab mob plab zis los ntawm oxytocin txhaj rau hauv ventral subiculum tshwm sim los ntawm kev nce ntxiv ntawm cellular glutamic acid hauv dialysate los ntawm ventral tegmental cheeb tsam, tab sis tsis los ntawm cov nucleus accumbens thiab yog antagonized los ntawm (+) MK-801, ib lub hwj chim uas tsis muaj sib tw los ntawm cov neeg tawm tsam ntawm cov NMDA subtype (Woodruff li al., 1987), txhaj rau hauv ventral tegmental tsam, tab sis tsis nyob rau hauv cov keeb kwm nucleus (saib daim duab 2 thiab Melis li al., 2009b) , nws yuav zoo dua yog tias cov kev tshawb nrhiav no ua rau kev ua kom muaj glutamatergic neurotransmission hauv cheeb tsam ventral tegmental, uas tig rau hauv mesolimbic dopaminergic neurons projecting rau nucleus accumbens. Seb puas muaj zog ntawm glutamic acid nyob hauv cheeb tsam ventral tegmental tom qab oxytocin txhaj rau hauv ventral subiculum tawm ntawm neurons pib hauv subiculum los yog lwm qhov chaw hauv hlwb (piv txwv li, prefrontal cortex) tsis paub tam sim no. Txawm li ntawd los, qhov no ua rau cov activation ntawm mesolimbic dopaminergic neurons thiab kev tso tawm ntawm dopamine nyob rau hauv lub nucleus accumbens. Ntawm no ua rau cov dopamine receptors ua rau cov kev ua ntawm incerto-hypothalamic dopaminergic neurons, tso dopamine nyob rau hauv paraventricular nucleus, ua li no activating oxytocinergic neurons projecting rau tus txha caj qaum thiab kev kho nruab nrab ntawm cov pob txha erection (saib saum toj no thiab Melis li al., 2007, 2009a; Succu li al., 2008).

2.4. Lub amygdala

Amygdala yog lwm lub paj hlwb hauv oxytocin fibres thiab receptors (saib Freund-Mercier li al., 1987; Vaccari et al., 1998; Uhl-Bronner et al., 2005). Oxytocin ntawm no yog xav kom muaj kev koom tes hauv kev sib txawv, los ntawm anxiolisis, kev cim xeeb thiab kev paub, kev txhawb zog rau kev kawm, kev xav hauv lub siab, kev xav lub ntsej muag thiab kev ntshai nyob rau hauv tib neeg mus rau erectile kev ua haujlwm thiab kev coj tus cwj pwm (saib Kondo et al., 1998; al., 2001; Ebner thiab lwm tus, 2005; Huber li al., 2005; Domes li al, 2007; Petrovic et al., 2008; Lee et al., 2009; Donaldson thiab Young, 2009; Hurlemann et al. , 2010). Txawm li cas los xij, lub peev xwm ntawm oxytocin los ntxias penile erection nyob rau hauv cov txiv neej nas thaum ntxias nyob rau hauv lub posteromedial cortical nucleus ntawm amygdala twb tshwm sim tsuas yog nyuam qhuav (Melis li al., 2009b). Cov lus teb tau tshwm sim ua ke nrog rau kev ntxiv rau ntawm tus xov tooj ntxiv dopamine nyob hauv lub dialysate uas tau los ntawm lub plhaub ntawm cov keeb kwm nucleus, raws li pom tom qab oxytocin txhaj rau hauv ventral subiculum (Melis li al., 2009b). Lub mechanism uas oxytocin txhaj rau hauv posteromedial cortical nucleus ntawm amygdala induces penile erection yog tsis paub hais tias lub caij. Cov ntaub ntawv muaj peev xwm qhia tau hais tias kev siv tshuaj tiv thaiv thiab kev ua kom tsis muaj zog nyob hauv lub dialysate uas tau los ntawm cov keeb kwm ntim khoom nruab ntug yog kho cov oxytocinergic receptors, vim ob lo lus teb raug tshem tawm ntawm oxytocin receptor antagonist d (CH2) 5Tyr ( Kuv) 2-Orn8-vasotocin txhaj rau hauv amygdala nucleus ob peb feeb ua ntej oxytocin (Melis li al., 2009b).

Xijpeem kho oxytocin activates nyob rau hauv posteromedial cortical nucleus ntawm lub amygdala, kev sib deev teb vim raug peptide yog tshem tawm los ntawm blockade ntawm tag nrho cov dopaminergic receptors nrog cis-flupenthixol txhaj rau hauv lub plhaub ntawm nucleus accumbens thiab los ntawm cov blockade ntawm NMDA receptors nrog ( +) MK-801 txhaj rau hauv ventral tegmental cheeb tsam, tab sis tsis mus rau hauv cov keeb kwm nucleus, raws li nrhiav rau cov pob qij txha raug tsim los ntawm oxytocin txhaj rau hauv ventral subiculum (Melis li al., 2009b). Qhov no qhia tau tias oxytocin txhaj rau hauv posteromedial nucleus ntawm amygdala activates glutamic acid neurotransmission hauv ventral tegmental thaj tsam. Qhov no ua rau nws pib ua rau ntawm mesolimbic dopaminergic neurons, ua rau cov pob txha txhav siv. Cov kev tshawb fawb qhia txog kev sib txuas lus neural ntawm kev sib txuas ntawm cov keeb kwm ntawm lub amygdala nrog lub ventral subiculum (Canteras li alien, 1995; Fabkis thiab Totterdell, 2003), cov kev tshawb nrhiav no nce tau tias qhov kev sib tshuam muaj nyob nruab nrab ntawm ob lub cheeb tsam ntawm lub hlwb, txoj hauv kev los ntawm amygdala los ntawm cov keeb kwm keeb kwm los yog hauv ventral tegmental tau piav qhia (Kelley thiab Domesick, 1982; Witter, 2006).

2.5. Tus txha caj qaum

Tus txha nqaj qaum yog lwm qhov chaw ntawm lub hauv siab lub cev uas muaj oxytocinergic fibres thiab receptors (Freund-Mercier thiab lwm tus, 1987; Uhl-Bronner et al., 2005), uas oxytocin induces penile erection (Tang et al., 1998 ; Veronneau-Longueville et al., 1999; Giuliano thiab Rampin, 2000; Giuliano et al., 2001). Raws li hais saum toj no, cov oxytocinergic fibers originate nyob rau hauv paraventricular nucleus ntawm cov hypothalamus thiab pab txhawb rau txoj hauv kev los tswj cov leeg txha spinal autonomic neurons mediating penile erection. Xwb cov fibers ua rau cov neeg sib xyaw ua ke nyob rau hauv dorsal horn preganglionic sympathetic thiab parasympathetic cell kab nyob rau hauv lub plhaus nkaug-lumbar thiab lumbo-sacral ib ceg nrog spinal neurons innervating penile cavernous corpora (Marson thiab McKenna, 1996; Giuliano thiab Rampin, 2000; Giuliano et al. , 2001). Cov kev sib txuas ntawm cov neeg hu ua tau pom los ntawm kev sau npe ntawm cov hlab ntsha paj hlwb ntawm tus qau thiab ncav qaum qaum nrog qog nqaij hlav qis rau hauv cavernous corpora, nrog ob qho tshuaj immuno-fluorescence thiab kev tshawb fawb laser microscopy (Tang et al., 1998; Veronneau-Longueville thiab al., 1999). Nyob hauv txoj kab nrog cov kev tshawb fawb no, hauv cov txiv neej niam txiv lub plab intrathecal txhaj tshuaj ntawm cov kab mob oxytocin ntawm lub lumbo-sacral, tab sis tsis nyob ntawm qhov kev tu-pob qij-lumbar, kev tawm hauv siab tuaj yeem nce siab hauv lub koob tshuaj. Cov teebmeem no tau raug tshem tawm los ntawm qhov blockade ntawm oxytocinergic receptor nrog d (CH2) 5-Orn2-vasotocin thiab ntawm lub plawv ntawm cov paj hlwb (Giuliano thiab Rampin, 8; Giuliano et al., 2000). Cov kev soj ntsuam no qhia tau hais tias oxytocin, ua rau ntawm lub lumbo-sacral spinal cord, tsub kom mob hlwb, thiab qhia tias oxytocin, tso tawm thaum lub cev ua rau lub cev muaj zog ntawm paraventricular nucleus yog ib lub zog activator ntawm spinal pro-erectile neurons projecting rau lub corporernous corpora. Interestingly, cov pro-erectile spinal neurons uas oxytocin ua rau siv nws cov nyhuv pro-erectile, kuj tau txais kev sib txuas ntawm serotoninergic neurons ntawm cov nucleus paragigantocellularis ntawm reticular tsim ntawm medulla oblongata (Marson thiab McKenna, 1992; Tang et al ., 1998). Txoj kev puas tsuaj ntawm cov kab mob no yog cov ejaculation thiab penile reflexes hauv cov txiv neej nas (Marson thiab McKenna, 1992; Yells li al., 1992). Vim tias cov tshuaj uas ua rau 5HT2C receptors pab txhawb kev siv tshuaj tiv thaiv thaum lub plab intracerebroventricularly, tiam sis tsis mus rau hauv qhov chaw parabentricular nucleus, thiab cov tshuaj uas thaiv 5HT2C receptors txo cov dopamine agonistand oxytocin hawbpem erection, thaum dopamine antagonists tsis txo 5HT2C agonist hawv penile erection saib Stancampiano thiab al., 1994 thiab cov neeg ua tim khawv nyob rau ntawd), nws tau raug pom tias oxytocin tswj qhov kev txiav txim ntawm pro-erectile 5HT2C receptors nyob rau theem ntawm lub lumbo-sacral spinal qord (Stancampiano li alien, 1994). Xwb, oxytocin feem xyuam rau txoj kev ua ntawm kev txheeb tus kab mob hauv cov hlab ntsha ntawm serotoninergic neurons los ntawm cov yeeb yam hauv nucleus paragigantocellularis, qhov twg cov neurons pib (saib Stancampiano li al., 1994).

3. Cov kev sib tshuam ntawm oxytocin, dopamine thiab glutamic acid nyob rau hauv lub hauv paus paj hlwb thiab penile erection

Raws li tau hais tseg hauv Tshooj 1, tag nrho cov oxytocinergic neurons tam sim no nyob rau hauv lub hauv paus hauv lub paj hlwb ntawm lub hauv paraventricular nucleus thiab lwm tus qauv. Cov kev ua ntawm cov neurons no yog nyob rau hauv kev tswj ntawm txawv neurotransmitters thiab / los yog neuropeptides. Cov feem kawm nyob rau theem siab yog dopamine, glutamic acid, gamma-aminobutyric acid (GABA), nitric oxide, endocannabinoids, opioid peptides, loj hlob hormone-release peptides, VGF-ntsig peptides thiab oxytocin nws tus kheej. Dopamine, glutamic acid, txoj kev loj hlob hormone tawm peptides, VGF-derived peptides thiab oxytocin yog stimulatory, xws li, cov compounds thiab lawv cov agonists pab rub penetration thaum txhaj rau paraventricular nucleus, thaum GABA, opioid peptides thiab endocannabinoids yog inhibitory, xws li, cov tshuaj los yog lawv cov agonists inhibit rab qaum erection (Saib Meisel thiab Sachs, 1994; Witt thiab Insel, 1994; Argiolas thiab Melis, 1995, 2004, 2005; Giuliano thiab Rampin, 2000, 2004; McKenna, 2000; Andersson, 2001; Hull et al., 2002).

Muaj ntau cov pov thawj ntawm cov pov thawj pom tias cov oxytocinergic neurons thiab cov saum cov neurotransmitters thiab neuropeptide muaj kev koom tes hauv kev tswj ntawm kev ua haujlwm erectile thiab kev coj tus cwj pwm ntawm kev sib txawv ntawm kev sib deev. Ntxiv thiab, oxytocin tso tawm hauv lwm qhov chaw hypothalamic hlwb, xws li thaj tsam ventral tegmental, hippocampus thiab nws cov cheeb tsam, cov amygdala thiab caj dab qaum yuav cuam tshuam rau cov kev ua ntawm cov neurons uas oxytocinergic synapses impinge. Thaum lub sij hawm no, tsuas yog ib qho tseem ceeb rau cov hlab ntaws ntawm cov hlab ntaws ntawm oxytocinergic synapses impinge, nrog qhov tseeb, yog lub cev ntawm mesolimbic dopaminergic neurons ntawm cov caudal ventral tegmental thaj tsam ntawm lub plhaub ntawm cov keeb kwm nucleus (Melis li al., 2007 , Hu ua Succu et al., 2008), thiab cov pro-erectile spinal neurons uas yog los ntawm txoj kab xev xaj xaj mus rau lub tuam txhab lub cev (saib Giuliano thiab Rampin, 2000; Giuliano et al., 2001) (saib tseem 2.2 thiab 2.5) . Muaj tseeb tiag, txawm hais tias muaj oxytocinergic synapses thiab receptors kuj tau pom nyob rau hauv ventral subiculum, amygdala thiab qaum qaum, thaj chaw uas txhua yam tseem ceeb rau kev siv tshuaj tiv thaiv kev laus (saib saum toj no), hauv cov cheeb tsam no hom neurotransmitter / s nyob rau hauv cov neurons ntawm uas oxytocinergic paj thaiv qhov kawg impinge, yog tseem tsis paub.

Qeb tshooj ntawm txoj kev tshuaj xyuas no piav qhia txog cov ntaub ntawv sau tseg ntawm cov tswv yim uas yog siv cov teebmeem ntawm oxytocin los ntawm cov caudal ventral tegmental, lub ventral subiculum ntawm hippocampus thiab nyob rau hauv cov leeg nrob qaum. Kev saib xyuas tshwj xeeb yog muab rau kev sib koom tes ntawm peptide nrog dopamine thiab glutamic acid nyob rau hauv cov cheeb tsam no thiab nyob rau ntawm lub luag hauj lwm no kev sib txuas ua si nyob rau hauv lub hauv paus tswj ntawm erectile Function. Ib qho lus qhia txog cov teebmeem ntawm dopamine thiab glutamic acid rau oxytocinergic neurons hauv paraventricular nucleus, uas tseem ua si lub luag haujlwm tseem ceeb nyob rau hauv erectile muaj nuj nqi yog muab thawj, kom tus nyeem ntawv paub txog lub xeev thaum ntxov ntawm kev tshawb fawb hauv daim teb no, raws li cov kev tshawb fawb no tau raug saib xyuas ntau heev (saib Argiolas thiab Melis, 1995, 2004, 2005; Melis thiab Argiolas, 2003). Tsis tas li no, tshwj xeeb yog muab rau cov ntsiab lus tsis ntev los no, uas tau hais txog lub luag hauj lwm tseem ceeb rau ob qho tib si dopamine-oxytocin txuas thiab glutamic acid-oxytocin txuas tsis tsuas yog kev sib deev (penile erection thiab copulation), tab sis tseem nyob hauv kev sib deev arousal thiab kev sib deev kev siab xav.

3.1. Dopamine-oxytocin kev sib cuam tshuam hauv kev sib txuas lus parabentricular

cov kev muaj peev xwm ntawm dopamine agonists kom induce penile erection by activating central oxytocinergic neurons tau pom tias tam sim ntawd tom qab nrhiav tau tias apomorphine induces penile erection thaum txhaj rau hauv paraventricular nucleus (Melis li al., 1987) thaum oxytocin receptor antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin txhaj intracerebroventricularly (icv) muaj peev xwm txo cov pob txha yuav luag tag nrho tsis yog los ntawm oxytocin muab icv, tab sis kuj yog apomorphine, muab subcutaneously (Argiolas li al., 1987b). Cov ntsiab lus tau ua raws li cov kev tshawb fawb qhia tau zoo xws li thaum d (CH2) 5Tyr (Me) 2-Orn8-vasotocin tau muab icv thiab apomorphine tau muab ncaj qha mus rau hauv cov leeg parabentricular nucleus (Melis et al, 1989b), leading kom hais tias dopamine agonists induce penile erection los ntawm activating paraventricular oxytocinergic neurons projecting mus ntxiv hypothalamic hlwb chaw thiab hauv particular rau cov leeg nrob qaum (saib Argiolas thiab Melis, 1995, 2004, 2005). Nyob rau hauv txoj kab nrog kev pom zoo no, nyob rau hauv kev ua kom pom cov kabmob, kev txwv ntawm lumbo-sacral oxytocinergic receptors los ntawm non-peptide oxytocin receptor antagonist tau nyuam qhuav pom muaj peev xwm tshem tau apomorphine-induced ris hauv intracavernous siab vim yog dopamine agonist apomorphine, muab pov thawj rau paraventriculo-spinal oxytocinergic txoj kev muab kev koom tes hauv kev siv tshuaj tiv thaiv kev ua pob ntseg (Baskerville li al., 2009).

Cov kev tshawb fawb hom phiaj ntawm kev txheeb xyuas ntawm dopamine reseptor lub luag hauj lwm rau qhov induction ntawm rab qau erection, ices tias tseem nyob rau hauv paraventricular nucleus dopamine receptor agonists induce penile erection los ntawm acting rau dopamine receptors ntawm lub tsev neeg D2, raws li muaj nyob nrog dopamine receptor agonists uas tau muab los ua (saib Melis li al., 1987; Eaton et al., 1991; Melis thiab Argiolas, 1995a). Raws li, apomorphine, muaj zog sib xyaw D1 / D2 receptor agonist, thiab quinpirole, muaj zog xaiv D2receptor agonist, tiam sis tsis yog SKF 38393, D1 receptor agonist, txhaj rau hauv no hypothalamic nucleus tau pom muaj induce penile erection nyob rau hauv lub koob tshuaj , thiab kev sib deev teb vim yog cov D2 tus neeg tau txais los ntawm cov tshuaj D2 tau raug tshem tawm los ntawm D23390 receptor antagonists, xws li haloperidol thiab l-sulpiride, tab sis tsis yog los ntawm SCH 1, tus D1987 receptor antagonist (Melis et al., 1999). Lub peev xwm ntawm apomorphine kom induce penile erection thaum txhaj rau hauv paraventricular nucleus kuj pom tseeb los ntawm cov kev tshawb nrhiav telemetry qhia tias dopamine agonist muab rau hauv paraventricular nucleus tau nce intracavernous siab hauv awake txiv neej nas tsis hloov modifying systemic ntshav (Chen et al. , 2001; Giuliano thiab Allard, 1999), raws li pom tom qab kev txhaj tshuaj (Bernabè et al., XNUMX). Cov kev tshawb fawb no kuj paub tseeb lub luag hauj lwm tseem ceeb ntawm D2 receptors, raws li D1 receptor agonists tau pom tias tsis tuaj yeem ua rau tsis tuaj yeem ua rau kom tsis tuaj yeem ua rau lub siab tawv thaum txhaj tshuaj mus rau hauv parabentricular nucleus (Chen li al., 1999).

Muaj ntau cov pov thawj ntawm cov ntawv pov thawj uas tau pom muaj hais tias Disturbed D2 receptors, uas nws txoj kev xav ua qog ua rau rab qaum erection, nyob rau ntawm lub cev ntawm oxytocinergic neurons. Ua ntej, cov nquab hu ua paraventricular muaj cov dopaminergic paj terminals uas tau hu ua incertohypothalamic dopaminergic neurons. Cov kab mob ntawm cov kab mob hauv hlwb no yog nyob hauv pawg A13 thiab A14 ntawm Dahlstrom thiab Fuxe (1964), ua rau ntau qhov chaw thiab muaj kev tiv thaiv ntau qhov kev kho mob hypothalamic, nrog rau cov kab mob paroxide classular oxytocinergic neurons rau cov leeg hlwb thiab / los yog lwm qhov chaw hypothalamic hlwb (Buijs et al., 1984; Lindvall et al., 1984).

Kev koom tes ntawm cov dopaminergic neurons nyob rau theem siab ntawm qhov kev tiv thaiv ntawm cov pob txha thiab kev tiv thaiv yog kev txhawb los ntawm kev tshawb fawb ntawm microdialysis uas qhia tau tias cov concentrations ntawm extracellular dopamine thiab 3,4-dihydroxyphenylacetic acid (DOPAC), nws cov metabolite loj, ntau zog hauv lub dialysate tau los ntawm qhov paraventricular nucleus ntawm kev sib deev muaj hwj chim hauv cov txiv neej uas qhia tias tsis siv tshuaj yaj yeeb thaum tsis muaj kev siv tshuaj ovarianectomised estrogen + progesterone-primed receptive poj niam (Melis li al., 2003).

Qhov nce ntawm dopamine thiab DOPAC concentrations tau ntau dua thaum luam yeeb nrog poj niam receptive (Melis li al., 2003), raws li muaj nyob rau hauv thaj tsam medial preoptic (Hull, al., 1995) thiab hauv nucleus accumbens (Pfaus thiab Everitt, 1995). Qhov ob, ntau cov kev tshawb fawb qhia tau tias penile erection vim raug yuam los ntawm kev tsim kho ntawm paroxetricular D2 receptors, yog kho los ntawm oxytocin tawm ntawm cov chaw no. Raws li, apomorphine txhaj rau koob tshuaj uas khaus penile erection, tau pom muaj peev xwm nce oxytocin concentration, tsis yog hauv cov ntshav ntawm cov nas thiab cov liab (Melis thiab lwm tus, 1989a; Cameron li al., 1992), tab sis kuj nyob rau hauv qhov hypothalamic hlwb cheeb tsam, xws li cov hippocampus (Melis li al., 1990). Nyob rau hauv txoj kab nrog cov ntsiab lus, apomorphine txhaj rau hauv paraventricular nucleus ntawm ib koob uas induces penile erection twb nyuam qhuav pom tau tias yuav tau nce ntxiv ntxiv ntawm cellular dopamine concentration hauv nucleus accumbens, cov nyhuv txo los ntawm oxytocin receptor antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin txhaj rau hauv thaj tsam ventral tegmental (Succu li al, 2007; Melis et al., 2009a) (saib tseem 4). Thib peb, ob sab ntawm cov hlwv ntawm cov hlab ntsha hauv cov hlab ntsha, uas yuav luag tag nrho tawm ntawm oxytocin los ntawm cov hypothalamic hlwb chaw (Hawthorn li al., 1985), tshem tawm apomorphine huav penile erection (Argiolas et al., 1987a), thiab xaiv cov oxytocin receptor antagonists muab tso rau hauv lub hauv paus rau sab hauv, tab sis tsis mus rau hauv paraventricular nucleus, txo dose-ua raws li cov tshuaj apomorphineinduced penile erection nrog lub hwj chim sib luag rau cov tshuaj no nyob rau hauv blocking oxytocin receptors (Melis li al., 1989b). Oxytocin receptor antagonists kuj tsis tshua muaj hwj chim nyob rau hauv kev txo cov cwj pwm ntawm cov txiv neej tus cwj pwm vim tsis yog oxytocin, tab sis kuj yog apomorphine (Argiolas li al., 1988, 1989).

Raws li lub tswv yim los ntawm D2 receptors qhib los ntawm dopamine los yog dopamine receptor agonists, ua rau kev ua ntawm oxytocinergic neurons, li no tso oxytocin hauv extrahypothalamic hlwb chaw thiab nyob rau hauv cov leeg nrob qaum, ntau heev cov ntaub ntawv support cov hypothesis tias qhov stimulation ntawm D2 receptors tsub kom cov concentration ntawm intracellular Ca2 + ions hauv lub cev ntawm lub cev ntawm oxytocinergic neurons, ua rau cov activation ntawm nitric oxide-synthase, Ca2 + -calmodulin-dependent enzyme, uas yog nyob rau hauv lub cev ntawm lub cev (Vincent thiab Kimura, 1992; Torres li al., 1993; Sanchez et al., 1994; Sato-Suzuki et al., 1998). Cov kab mob qoob loo ntau dua tuaj ua rau lub sijhawm ua rau lub cev muaj sia nyob rau ntawm oxytocinergic neurons. Raws li, (1) apomorphineinduced penile erection yog tiv thaiv los ntawm cov organic calcium channel blockers thiab by_-conotoxin GVIA, lub zog thiab xim blocker ntawm tus kabmob Caij Qis Ca2 + raws ntawm N-hom (McCleskey li al., 1987), muab rau hauv cov chaw ua si nucleus (saib Argiolas li al., 1990, thiab cov lus nug nyob hauv); (2) apomorphine huav penile erection yog tiv thaiv los ntawm nitric oxide-synthase inhibitors muab rau hauv paraventricular nucleus (Melis li al., 1994c); thiab (3) apomorphine thiab lwm yam tshuaj D2 tus neeg mob hnyav uas tau muab rau cov koob tshuaj tiv thaiv kab mob qis qis rau nitric oxide ntau zog hauv qhov kev sib txuas lus hu ua intra-cerebral microdialysis, nce ntxiv uas yog txo los ntawm cov neeg ua rau cov tshuaj nitrav oxide-synthase D2 receptor agonistinduced penile erection (Melis li al., 1996). Lub tswv yim los ntawm kev siv cov nitric oxide activates paraventricular oxytocinergic neurons, tseem tsis paub, tab sis muaj cov ntaub ntawv hais tias nitric oxide ua raws li tus neeg xa xov xwm intracellular thiab cov guanylate cyclase tsis koom tes. Xwb, lub phosphodiestereresistant analogue ntawm cyclic GMP, 8-bromo-cyclic GMP, tau pom tias tsis tuaj yeem ntxias penile erection thaum muab rau hauv paraventricular nucleus (daim duab 2) (saib Melis thiab Argiolas, 1995b thiab cov lus nug nyob hauv).

Cov txhais lus saum toj no tau raug feem ntau tsis yog kev ntseeg, feem ntau vim hais tias lub stimulation ntawm dopamine D2 receptors feem ntau yog sib npaug rau inhibition es excitation ntawm lub cev ntawm lub hlwb ntawm cov neurons uas muaj cov receptors los ntawm kev sib txawv G protein protein coupled mechanisms (saib Sokoloff thiab Schwartz, 1995). Txawm li cas los xij, ib qho kev piav qhia txog qhov tsis sib haum, uas yog nyob rau ntawm txoj kev ncaj qha los ntawm kev siv dag zog ncaj qha ntawm paraventricular oxytocinergic neurons los ntawm dopamine, tau pom tias tsis ntev los no los ntawm kev nrhiav tau ntawm ib G protein-coupled dopamine D4 (D2, D2 thiab D3), lub stimulation ntawm uas nce Ca4 + influx hauv xov tooj ntawm cov tshuaj npaj muaj ib lub cim cloned ntawm no receptor subtype (Moreland li al., 2). Qhov tseem ceeb tshaj plaws, kev xaiv D2004 receptor agonist (xws li, ABT 4) (N-methyl-724- (4-cyanophenyl) piperazynil-2methylbenzamide maleate) muaj peev xwm pom muaj peev xwm ntawm kev ua rau cov txiv neej tsis muaj zog thaum txiv neej (Brioni li al., 3). Cov nyhuv no tsis pom muaj nrog D2004 tus neeg mob reseptor subtype agonist PNU-2E (R-95666-dihydro-N, N-dimethyl-5,6Himidazo [4-i] quinolin-4,5,1-amine) (Hsieh et al., 5), uas kuj tsis tuaj yeem tsis tuaj yeem nce Ca2004 + tshooj hauv cov xovtooj ntawm tes uas muaj lub npe ntawm D2 tus neeg tau txais kev xa ntawv (Brioni li al., 4; Moreland thiab al., 2004). Nyob rau hauv txoj kab nrog cov lus saum toj no thiab kev tshawb pom, PD 2004 (N-methyl-168,077- (4-cyanophenyl) piperazynil-2methylbenzamide maleate), PIP-3EA (3- [2- (4-methoxyphenyl) piperazin-2-ylmethyl] imidazo [1-a] pyridine) thiab lwm yam tshuaj D1,2 receptor agonists (Heier et al., 4; Melis et al., 1997b; Löber et al., 2006), tau pom muaj qee zaum rab qau thaum txhaj tshuaj tawm, icv thiab ua qhov paraventricular nucleus, tab sis tsawg dua zoo dua apomorphine. Cov teebmeem pro-erectile ntawm cov D2009 receptor agonists tau tiv thaiv los ntawm L-4 (745,870- [chlorophenyl] piperazin-3-yl) -methyl-4H-pyrrolo [1-B] pyridine trihydrochloride), ib qho D1 receptor antagonist (Patel li al., 2,3; Melis li al., 4, 1997b; Löber et al., 2005).

Thaum kawg, cov nyhuv pro-erectile ntawm cov D4 receptor agonists saum no kuj tau txo los ntawm nitric oxide-synthase inhibitors, muab rau hauv paraventricular nucleus, thiab by d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, ib qho selective oxytocin receptor antagonist muab icv tab sis tsis nyob hauv paraventricular nucleus. Cov kev soj ntsuam no muaj nyob rau hauv txoj kab nrog cov hypothesis uas D4 receptor agonists tseem hnia oxytocinergic neurons los ntawm activating nitric oxide-synthase, thiab tso oxytocin hauv extrahypothalamic hlwb thaj chaw, uas nyeg pab penile erection, raws li qhia rau apomorphine thiab classical D2 agonists (Melis et al ., 2005, 2006b; Löber et al., 2009).

Cov lus saum toj no kuj txhawb qhov kev ntseeg tias dopamine induces penile erection los ntawm ua rau D4 receptors nyob rau ntawm lub cev ntawm lub cev ntawm paraventricular oxytocinergic neurons, thiab ua rau kom muaj zog Ca2 + influx mus rau hauv lub cev ntawm oxytocinergic neurons, uas ua rau cov tshuaj nitric oxide ntau dua. Nitric oxide nyeg qhib oxytocinergic neurons tso tawm cov kab mob oxytocin hauv hypothalamic hlwb nrawm thiab hauv cov leeg nrob qaum, zoo li twb tau sib tham lawm. Hauv qhov no, nws yog qhov tseem ceeb tshaj plaws tias dopamine receptors tau raug txheeb xyuas nyob rau hauv lub cev ntawm lub cev ntawm oxytocinergic neurons nyob rau hauv paraventricular nucleus tsuas yog nyuam qhuav los ntawm kev tshawb fawb txog immuno-fluorescence nrog cov roj ntsha siab D2, D3 thiab D4 lub cev tiv thaiv kab mob thiab nrog oxytocin antibodies. Cov kev tshawb fawb no tau qhia txog tag nrho peb lub D2receptor subtypes (D2, D3 thiab D4), uas sib koom ua ke nyob rau hauv lub cev ntawm lub cev ntawm oxytocinergic neurons nyob rau hauv qhov paraventricular nucleus (thiab tseem nyob rau hauv kev sib deev succaoptic thiab thaj tsam thaj tsam mob ntsws) (Baskerville thiab Douglas, 2008; Baskerville li al., 2009).

Qhov no muab kev pabcuam muaj zog neuroanatomical kom tau tias dopamine thiab dopamine receptor agonists ntawm D2 hom induce penile erection los ntawm activating ncaj qha oxytocinergic neurons projecting mus rau extrahypothalamic hlwb chaw recalled saum toj no, xws li, tus txha nqaj qaum, thaj tsam ventral tegmental, hippocampus thiab cov amygdala. Txawm li cas los xij, cov kev tshawb pom no tsis muab kev pab rau qhov kev txheeb xyuas ntawm D2 tus neeg tau txais tos subtype / s, uas nws txoj kev xav tau ua rau lo lus teb erectile. Hmoov tsis, tsis muaj kev pab yuav tau txais txawm los ntawm cov kev tshawb fawb tsom kom paub cov oxytocinergic neurons pib los ntawm dopamine receptor agonists nyob rau hauv paraventricular nucleus. Muaj tseeb tiag, tis ntawm qhov txawv ntawm kev ua rau ntau yam dopamine receptor subtypes, xws li sib xyaw dopamine receptor agonists (xws li, apomorphine), lossis D2 receptor agonists (xws li, quinpirole, uas ua rau txhua D2 receptor subtypes) lossis D4 receptor agonists qhov ua kom muaj oxytocinergic neurons, raws li ntsuas los ntawm qhov nce ntawm FOS protein nyob rau hauv parvocellular oxytocinergic neurons ntawm paraventricular nucleus (Bitner li al., 2006). Txawm li cas los xij, qhov kev tshawb pom no tau raug nyuam qhuav nug, raws li FOS protein nce nyob rau hauv paraventricular oxytocinergic neurons tau pom thaum tsuas yog thaum cov pob txha txhaws tau raug ua los ntawm quinerolane, uas ua los ntawm D2 thiab D3 receptor subtypes, tab sis tsis yog PD 168077, D4 receptor agonist, nyob rau hauv kev phem ntawm lub peev xwm ntawm ob lub tebchaw mus ntxias kev sib deev teb (Baskerville li al., 2009).

Ntxiv thwmsim nrog xaiv cov agonists ntawm lwm D2 receptor subtypes (tsuas yog D2 thiab D3) yog li tsim nyog los txheeb xyuas lub luag hauj lwm ntawm txhua tus dopamine receptor subtype hauv kev tswj ntawm kev ua haujlwm ntawm erectile nyob rau theem siab. Nyob rau hauv qhov no, raws li twb tau rov qab ua ntej, apomorphine, uas ua rau xam pom txhua tus dopamine receptor subtypes (saib Brioni li al., 2004, thiab references nyob rau hauv), zoo dua li D4 receptors agonists hauv inducing penile erection thaum txhaj rau hauv paraventricular nucleus. Qhov no tej zaum yuav piav qhia los ntawm tus affinity affinity ntawm apomorphine rau D4 receptors thaum piv rau ntawm D4 receptor agonists, los yog hloov, D4 receptor agonists yuav ua tau raws li D4 receptor nrab agonists, los yog ua kom sib txawv ntawm dopamine receptor subtypes los ntawm apomorphine tsim dua ib qho kev ua rau ntawm oxytocinergic neurons mediating penile erection, dua li cov activation ntawm D2 receptor agonists ntawm D4 receptor subtype nkaus xwb.

Cov kev sib tshuam ntawm dopamine D1 thiab D2 receptors tau raug piav nyob rau hauv kev tswj ntawm kev sib deev tus cwj pwm nyob rau theem ntawm thaj tsam ntawm thaj chaw nruab nrab (saib Hull li al., 1989). Nyob rau hauv rooj plaub uas tsis muaj peev xim ntawm D2 tus neeg tuaj yeem kho lub cev (Hsieh et al., 2004) yuav raug lees paub (tab sis saib Depoortère et al., 2009), piv txwv li txawm tias tom qab kev txhaj tshuaj ntawm cov sib txuas rau hauv cov kev sib tw paraventricular nucleus , lub luag hauj lwm loj rau D3 receptors ib leeg los nrog ua ke nrog D4 receptors nyob rau hauv kev ua rau ntawm oxytocinergic neurons mediating penile erection yuav tsum tau soj ntsuam xyuas txhua yam (saib Baskerville li al., 2009). Hmoov tsis, Xaiv D2 thiab D3 cov khoom noj txom nyem agonists (piv txwv li, qhov sib txawv hauv lawv qhov kev sib raug zoo rau cov ob leeg txais kab mob tsawg kawg plaub / tsib xaj ntawm qhov ntau hauv vitro) tsis muaj rau lub sijhawm. Vim li no, cov lus qhia tsis ntev los no tias D3 receptors nruab nrab cov tub rog erection induced los ntawm classical D2 receptor agonists, uas yog raws li ntawm kev muaj peev xwm ntawm kev muaj peev xwm ntawm D3 receptor antagonists ua nyob rau hauv cov tshuaj thev hauv vitro, los txo cov pob txha erection induced by classical D2 agonists, xws li apomorphine, quinpirole thiab pramipexole, uas txaus siab qhib tag nrho cov dopamine D2 receptor subtypes (Collins li al., 2009), cov kev xav tau yeej siv tau nrog lwm cov kev sim. Qhov kev cai no tseem ceeb heev vim hais tias tsis muaj kev cuam tshuam ntawm D4 tus neeg tau txais kev hnyav rau ntawm kev tshawb fawb no tau pom nyob rau hauv txoj kev tshawb no, hauv kev sib txawv ntawm qhov kev tshawb fawb tau teev saum toj no, uas ua rau muaj kev cuam tshuam ntawm D4 receptor agonists. Xwb, txawm tias muaj peev xwm ntawm apomorphine los ntxias rab qau erection (thiab yawning) nyob rau hauv D4 receptor knockout nas nrog ib tug potency zoo tib yam rau uas pom cov tsiaj qus hom D4 receptor knockout nas thiab lub peev xwm ntawm D3 receptor antagonists los mus tshem tawm cov apomorphine teb rau cov tsiaj txhu ( Collins thiab lwm tus, 2009) tsis tuaj yeem pom tias yog ib qho pov thawj rau kev xaiv ntawm D3 tus neeg tau txais kev xa subtype nyob hauv D2 tus neeg tau txais kev pabcuam los ntawm kev ua haujlwm rau cov laus. Cov hom kev sib txawv txawv, sib tw nrog neurotransmitter / neuropeptide thiab / los yog neurotransmitter / neuropeptide receptor gene ablation (neurotransmitter / neuropeptide thiab / los yog neurotransmitter / neuropeptide receptor knockout animals) muaj feem ntau ntxiv tsis meej pem thiab muaj teeb meem hauv kev pom zoo ntawm kev sib deev kev ua haujlwm ntawm cov neurotransmitters thiab / los yog neuropeptide thiab lawv cov neeg txais tos. Namely, oxytocin noob ablation ua rau oxytocin khob tawm cov nas uas tus niam txiv thiab copulate feem ntau, xws li yog oxytocin tsis ruaj rau mating thiab copulation. Tsis tas li cov homozygous poj niam oxytocin knockout nas qhia tau hais tias mating thiab koom tes, txawm tias nrog ib qho cim tsis zoo ntawm cov mis downdown (Nishimori li al., 1996; Young et al., 1996). Ablation ntawm tus noob encoding neuronal nitric oxide synthase, kuj ua nitric oxide synthase khob tawm cov nas uas koj tus txij nkawm thiab copulate feem ntau (Huang et al., 1993). Txawm li cas los xij, cov kev tshawb pom no tej zaum yuav qhia txog qhov tseem ceeb ntawm kev ua haujlwm ntawm kev ua haujlwm ntawm lub cev, piv txwv li, qhov rov ua haujlwm ntawm qhov kev sib txuas lus hauv nws txoj kev tswj hwm ntawm theem nruab nrab thiab ib ncig ntawm ib sab.

Xws li rov qab tau muaj ib qho evolutionary keeb kwm, txij li nws guarantees lub tso cai ntawm cov noob mus rau lwm tiam rau cov ciaj sia taus ntawm cov tsiaj. Yog li, qhov tseeb tias ablation ntawm D4 receptor gene tsis hloov cov nyhuv pro-erectile ntawm apomorphine, pom tias D4 receptors, xws li oxytocin thiab nitric oxide, tsuas yog ob peb ntawm cov neeg tuaj ua haujlwm ua haujlwm hauv lub tshuab tswj kev ua haujlwm erectile, tsis yog tawm tswv yim hais tias tsis muaj lub luag hauj lwm rau cov neeg txais kev pom zoo hauv kev tswj ntawm rab qaum erection thiab kev coj tus cwj pwm. Tsis ua hauj lwm ntawm D4 agonists kom induce penile erection thaum muab systemically rau cov txiv neej cov kaus poom sib txawv hom nyuam qhuav tau qhia los ntawm lwm txoj kev tshawb nrhiav (Depoortère li al., 2009). Txawm li cas los, hauv qhov txawv ntawm kev ua haujlwm ntawm Collins li al. (2009), thiab los ua daim duab ntawm D2 tus cwj pwm txawv subtypes hauv kev tswj ntawm rab qaum erection txawm ntau puzzling, txoj kev tshawb no kuj qhia tau hais tias cov kws kho hniav xaiv D3 tus kab mob antagonists uas tau muab tawm tau tsis tuaj yeem txo qhov ua rau apomorphine hawv penile erection hauv txiv neej nas ntawm lub lim ntau dua rau cov pro-erectile nyhuv ntawm apomorphine, thaum kev sib deev teb (thiab yawning) yog antagonized los ntawm kev xaiv D2 antagonist L-741,626 (3 - [[4- (4-chlorophenyl) -4-hydroxypiperidin -1-yl] methyl-1H-indole), ua rau tus sau phau ntawv xav kom D2 receptors, tsis yog D3 thiab D4 cov neeg tuaj yeem, yog cov ua si lub luag hauj lwm loj hauv D2 agonist hawv penile erection (Depoorter thiab lwm yam, 2009). Thaum kawg, tseem tias qhov excitatory nyhuv ntawm dopamine receptor agonists ntawm oxytocinergic neurons mediating penile erection, tsawg kawg yog ib feem, yog indirect es tsis ncaj, xws li, kho los sis cuam tshuam los ntawm kev hloov hauv cov kev ua ntawm lwm cov neurotransmitters neuropeptides tau hloov cov kev ua ntawm oxytocinergic neurons nyob rau hauv paraventricular nucleus, tsis tau tag nrho txiav tawm.

3.2. Glutamic acid-oxytocin kev sib cuam tshuam hauv kev sib txuas ntawm parabentricular nucleus

Cov pa nchuav ntawm qhov hypothalamus yog cov nplua nuj nyob hauv kev sib xyaw nrog uas muaj cov tshuaj amino acid ua ib qho neurotransmitter (xws li, glutamic acid thiab aspartic acid) (Van Den Pol, 1991). Excitatory amino acids nyob rau hauv no nucleus muaj kev koom tes nrog ntau yam kev khiav dej num, xws li rab yaj zuaj erection thiab kev sib deev tus cwj pwm (Roeling li al., 1991; Melis et al., 1994b, 2000, 2004b). Raws li, N-methyl-d-aspartic acid (NMDA), tus xaiv agonist ntawm NMDA receptor subtype, tiam sis tsis (±) -_- amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) , tus xaiv agonist ntawm AMPA receptor subtype lossis (±) -trans (1) -amino-1,3-cyclopentane dicarboxilic acid (ACPD), xaiv cov agonist ntawm metabotropic receptor subtype, muaj peev xwm pom muaj peev txheej ntawm rab qau erection thaum txhaj tshuaj paraventricular nucleus ntawm cov nas tsuag ywj pheej (Melis li al., 1994b). 948 MR Melis, A. Argiolas / Neuroscience thiab Biobehavioral Reviews 35 (2011) 939-955 NMDA raug tiv thaiv los ntawm (+) MK-801, tus NMDA reseptor antagonist (Woodruff li al., 1987 ), txhaj rau hauv paraventricular nucleus (Melis li al., 1994b). Nyob rau hauv txoj kab nrog cov ntsiab lus no, hauv cov kev tshawb nrhiav telemetry tsom xyuas kev ceev nrhau intracavernous siab, NMDA tau pom muaj ntau dua li cov agonists ntawm lwm cov excitatory amino acid receptor subtypes thaum txhaj rau hauv paraventricular nucleus hauv kev nce siab hauv pob ntseg los yog cov txiv neej niam txiv (Zahran et al., 2000; Chen thiab Chang, 2003).

Raws li tau hais los saum toj no rau oxytocin thiab dopamine, nws yuav hais tias NMDA receptors mediating penile erection nyob hauv lub cev ntawm oxytocinergic neurons, vim excitatory amino acid paj xaus impinge rau ntawm oxytocinergic cell lub cev nyob rau hauv cov paraventricular nucleus (Van Den Pol, 1991). Nyob rau hauv qhov sib piv nrog dopamine receptor agonists, cov nyhuv pro-erectile ntawm NMDA yog thaj mediated los ntawm kev ua rau ntawm oxytocinergic neurotransmission, raug tshem tawm ntawm cov oxytocin antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin icv, tab sis tsis yog rau hauv qhov chaw parabentricular nucleus (saib Argiolas thiab Melis, 1995, 2004, 2005 thiab cov lus qhia nyob hauv). Ib yam li, NMDA hos ua kom muaj oxytocinergic neurotransmission kuj tseem ua rau kev ua rau nitric oxide-synthase, vim NMDA hawv penile erection yog tiv thaiv los ntawm nitric oxide-synthase inhibitors (N-Nitro-N-methyll-arginine methyl ester thiab N- methyl-thio-l-citrulline) muab rau hauv paraventricular nucleus, thiab NMDA raug txhaj rau hauv parabentricular nucleus nyob rau hauv koob tshuaj uas induce penile erection, tsub kom nitric oxide ntau lawm hauv hypothalamic nucleus (saib Argiolas thiab Melis, 1995, 2004, 2005 thiab cov references nyob rau ntawd ). Raws li rau dopamine receptor agonists, lub NMDA vim raug yuam ua rau cov nitric oxidesynthase kuj tseem tuaj yeem nce ntxiv Ca2 + influx hauv oxytocinergic ntawm lub cev los ntawm Ca2 + channel-coupled NMDA receptors, raws li muaj nyob hauv ntau cov neural preparations (rau kev ntsuam xyuas saib Snyder, 1992; Southam thiab Garthwaite, 1993; Schuman thiab Madison, 1994 thiab cov lus nug nyob hauv). Nitric oxide nyeg qhib oxytocinergic neurotransmission (saib saum toj no). Lub hauv paus chiv keeb ntawm glutamatergic qhov projections uas qhib cov txheej txheem parventricular oxytocinergic neurons mediating penile erection yog tsis paub, txawm tias qee tus neuroanatomical thiab electrophysiological pov thawj qhia tias lawv yuav pib, tsawg kawg yog ib feem, hauv hippocampus (Saphier thiab Feldman, 1987; Chen et al., 1992) . Txawm hais tias kev ua hauj lwm ntxiv yog qhov yuav tsum tau ua kom zoo dua qhov keeb kwm ntawm glutamatergic projections mus rau paraventricular nucleus, kev koom tes ntawm glutamic acid nyob rau hauv paraventricular nucleus nyob rau hauv kev tswj ntawm penile erection thiab kev coj tus cwj pwm yog kom meej los ntawm microdialysis cov kev tshawb fawb. Raws li, qhov ntxiv ntawm cellular concentrations of glutamic acid thiab aspartic acid tau nce hauv cov dialysate tau los ntawm paraventricular nucleus ntawm cov txiv neej nas uas qhia cov tshuaj tsis muaj kab mob thaum tso rau hauv qhov muaj cov tshuaj tsis ua hauj lwm + progesterone-primed receptive pojniam nas (Melis li al., 2004b), penile erections uas tseem kho tau los ntawm kev ua kom muaj kev sib kis ntawm cov kab mob oxytocinergic (Melis li al., 1999a, b). Cov kev nce no tau pom muaj ntau dua thaum luam yeeb nrog tus poj niam uas tau txais kev pom zoo (Melis li al., 2004a). Nyob rau hauv txoj kab uas pom tias qhov kev ua kom muaj zog ntawm cov amino acids tshwm sim hauv cov kev sib tw paraventricular thaum lub sij hawm siv tshuaj tua kab mob thiab kev sib txuas lus, ob leeg tsis siv tshuaj thiab tus cwj pwm (thaum lub sij hawm nyob rau hauv copula penile erections tshwm sim) txo los ntawm blockade ntawm NMDA receptors nyob rau hauv paraventricular nucleus , thiab qhov kev txo qis no yog ua raws li kev txo qis ntawm nitric oxide ntau lawm uas tshwm sim nyob rau hauv qhov kev sib txuas ntawm cov pa roj hypothalamic nyob rau cov kev mob ntawm lub cev (Melis li al., 2000). Ib qho kev nce rau hauv cov txheej txheem glacamic acid ntau ntxiv rau kev poob GABA tso tawm ntawm GABAergic paj hlwb kawg ntawm kev ua haujlwm ntawm cov kab mob cancer acidic synthesized nkaus rau cov kab mob oxytocinergic lub cev, kuj pom muaj nyob rau hauv qhov paraventricular nucleus tom qab qhov blockade ntawm cannabinoid CB1 receptors los ntawm CB1 antagonist SR 141761A, muab tso rau hauv cov pos hniav los yog ncaj qha mus rau hauv cov leeg nquab ntawm cov koob tshuaj uas ua rau lub plab zom erection (saib Succu et al., 2006; Castelli et al., 2007). Xws li qhov kev coj ua rau cov activation ntawm nitric oxide-synthase nyob rau hauv lub cev ntawm lub cev ntawm oxytocinergic neurons, nce nitric oxide ntau lawm. Nitric oxide nyeg qhib oxytocinergic neurons kom kho cov pob qij txhav raws li piav saum toj no. Nyob rau hauv txoj kab nrog txoj kev mechanism, SR 141761A vim khaus penile erection raug txo los ntawm blockade ntawm NMDA receptors thiab cov nitric oxide-synthase inhibitors, tab sis tsis yog lub blockade ntawm dopamine los yog oxytocin receptors nyob rau hauv paraventricular nucleus, thaum nws tiv thaiv los ntawm cov blockade ntawm central oxytocin receptors los ntawm oxytocin receptor antagonists muab icv

3.3. Oxytocin-dopamine kev sib cuam tshuam hauv cheeb tsam ventral tegmental

Oxytocin induces penile erection thaum txhaj rau hauv cov caudal ntawm thaj tsam ventral tegmental hauv ib koob tshuaj (Melis li al., 2007). Qhov qis tshaj plaws txhaj koob tshuaj txhaj koob tshuaj tiv thaiv yog 20 ng, thaum lub siab tshaj plaws koob tshuaj yog 100 ng. Cov nyhuv oxytocin yog kho kom haum ntawm oxytocinergic receptors, raws li kev sib deev lo lus yog tshem tawm los ntawm kev txhaj tshuaj tiv thaiv ntawm oxytocin antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin hauv cheeb tsam vaud teg haujlwm. Cov receptors yog nyob hauv lub cev ntawm lub cev ntawm dopaminergic neurons, uas yog tsim los ntawm lub plhaub ntawm nucleus accumbens. Li no, (1) cov kev tshawb fawb lab kuaj immuno-fluorescence qhia tau tias nyob rau hauv cov caudal ventral tegmental cheeb tsam oxytocinergic fibers yog nyob ze ze nrog lub cev ntawm dopaminergic neurons, feem ntau ntawm cov uas tau zoo tias muaj npe rau tyrosine-hydroxylase thiab muaj retrograde tracer Fluorogold yav dhau los (Melis li al., 2007), thiab (2) ventral tegmental tsam oxytocin huas penile erection tshwm sim nrog rau kev nce hauv concentration ntawm ntxiv-cellular dopamine nyob rau hauv dialysate tau los ntawm lub plhaub ntawm lub nucleus accumbens (Melis li al., 2007). Oxytocin huas penile erection kuj tshwm sim nrog ntau zuj zus hauv nitric oxide ntau lawm hauv ventral tegmental, yog ob qho lus teb antagonized tsis tsuas yog d (CH2) 5Tyr (Me) 2-Orn8-vasotocin thiab los ntawm nitric oxide synthase inhibitor S- methyl-thio-l-citrulline, tab sis kuj yog _-conotoxin, muaj roj-dependent Ca2 + raws blocker, thiab los ntawm ODQ (1H- [1,2,4] oxadiazole [4,3-a] quinoxaline-1-ib), lub hwj chim inhibitor ntawm guanylate cyclase, tag nrho cov muab hauv cov caudal ventral tegmental ua ntej oxytocin (Succu li al., 2008). Raws li Fluorogold tau sau tias dopaminergic cell lub cev raug hu los ntawm oxytocinergic fibers, pom tau tias zoo rau tyrosine hydroxylase nyob rau hauv cov caudal ventral tegmental, tau zoo tib yam hais txog nitric oxide-synthase thiab guanylate cyclase (Succu et al., 2008), oxytocin -caus phom penile erection tej zaum yuav kho los ntawm cov nram qab no mechanism. Kev xyuam xim ntawm oxytocinergic receptors nyob rau hauv dopaminergic cell lub cev los ntawm peptide nce Ca2 + influx hauv lub cev ntawm dopaminergic neurons. Qhov no ua rau cov nitric oxide-synthase, Ca2 + -calmodulin-dependent enzyme, ua li cov roj nitric oxide ntau lawm. Nitric oxide nyeg pib ua guanylate cyclase, ua rau kom muaj zog ntawm cov kab GMob cyclic. Cyclic GMP activates dopaminergic neurons projecting rau cov nucleus accumbens. Lub luag hauj lwm ntawm cyclic GMP hauv rab qaum erection induced los ntawm oxytocin txhaj rau hauv caudal ventral tegmental thaj av ntawd kuj txaus siab los ntawm kev muaj peev xwm ntawm 8-bromo-cyclic GMP, ib tug active phosphodiesterase-resistant analogue cyclic GMP, induce penile erection thaum txhaj rau hauv cov caudal ventral tegmental, thiab kom ntxiv cov cellular dopamine hauv dialysate los ntawm cov nucleus accumbens (Succu et al., 2008; Melis et al., 2009a). Qhov no yog nyob rau ntawm txoj kab nruab nrab ntawm cov cuab yeej ua los ntawm nitric oxide activates oxytocinergic neurons hauv paraventricular nucleus, 8-bromo-cyclic GMP tsis induce penile erection thaum txhaj hauv no nucleus (Melis thiab Argiolas, 1995b) (Fig. 2). Raws li cov neural txoj kev qhib los ntawm dopamine nyob rau hauv lub nucleus accumbens ua rau penile erection, cov no tseem tsis paub. Txawm li cas los xij, cov ntaub ntawv qhia tau hais tias cov kev no ua rau dopamine neurotransmission nyob rau hauv qhov chaw paraventricular nucleus ntawm hypothalamus. Li no, oxytocin huas penile erection tshwm sim concomitantly kom muaj nce hauv ntxiv-cellular dopamine tsis tsuas yog nyob rau hauv lub nucleus accumbens, tab sis kuj nyob rau hauv paraventricular nucleus, thiab yog antagonized los ntawm dopamine receptor antagonist haloperidol txhaj rau hauv paraventricular nucleus (Melis li al., 2007). ASib tw ua ke, cov ntsiab lus no txhawb qhov kev xav tias oxytocinergic neurons pib tawm hauv cov kev sib txuas lus parabentricular thiab projecting rau qhov caudal ventral tegmental, thaum qhib tso tawm oxytocin hauv cheeb tsam no, ua li no activating tsis-cyclic GMP signaling system, uas nyob rau hauv lem activates mesolimbic dopaminergic neurons (Melis li al., 2007, 2009a; Succu li al., 2008). Dopamine tso tawm rau hauv cov nucleus accumbens nyob rau hauv lem activates neural txoj kev ua rau cov ua kom muaj kev sib raug zoo ntawm incerto-hypothalamic dopaminergic neurons, uas tsim kho paraventricular oxytocinergic neurons projecting rau tus txha caj qaum mediating penile erection. Nyob rau tib lub sijhawm, dopamine tso tawm rau hauv paraventricular nucleus tej zaum kuj qhib oxytocinergic neurons projecting rau hypothalamic hlwb chaw xws li ventral tegmental cheeb tsam, hippocampus, amygdala thiab kab tias tsam lwm qhov chaw ntawm lub hlwb.

Raws li tau hais los saum no, nyob rau hauv cov kab uas muaj qhov kev pom zoo no, apomorphine txhaj rau hauv paraventricular nucleus ntawm ib koob uas induces rab qaum erection kuj nce ntxiv cellular dopamine concentration hauv nucleus accumbens, cov nyhuv txo los ntawm oxytocin receptor antagonist d (CH2) 5Tyr (Me ) 2-Orn8-vasotocin txhaj rau hauv ventral tegmental thaj tsam (Succu li al., 2007; Melis et al., 2009a). Ua ke, cov kab mob neural saum toj no yuav ua rau lub nruab nrab ntawm cov hlab ntsha hauv siab nees nrog dopamine, oxytocin thiab lwm cov neurotransmitters (xws li, glutamic acid, pom hauv qab) cuam tshuam tsis yog kev sib deev kev ua haujlwm xwb, tab sis kev sib deev kev txhawb zog thiab kev sib deev (saib Tshooj 4).

3.4. Oxytocin-glutamic acid sis nyob hauv ventral subiculum ntawm hippocampus

Oxytocin induces penile erection thaum txhaj rau hauv ventral, tab sis tsis nyob hauv dorsal subiculum, nyob hauv ib koob tshuaj (Melis li al., 2009b). Kev sib deev lo lus yog kho kom haum ntawm oxytocin receptors, raug tshem tawm los ntawm kev txhaj tshuaj tiv thaiv ua ntej (XXXUMX) 2-Orn5-vasotocin uas tau muab tso rau hauv tib qho chaw oxytocin, raws li muaj nyob hauv lwm qhov chaw hauv lub hlwb (saib saum toj no) . Raws li lub zos ntawm cov receptors, cov ntaub ntawv qhia tau hais tias lawv nyob hauv lub cev ntawm lub cev ntawm cov neurons nplua nuj nyob hauv nitric oxide-synthase.

Raws li, kev tshawb fawb microdialysis qhia tau hais tias oxytocin huas penile erection tshwm sim ua ke nrog kev nce hauv nitric oxide ntau lawm hauv ventral subiculum, thiab qhov nce no yog tshem tawm tsis tas ntawm qhov kev txhaj tshuaj ua ntej ntawm nitric oxidesynthase inhibitor S-methyl-thio-l-citrulline thiab los ntawm nitric oxide scavenger hemoglobin, tab sis kuj los ntawm d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, tag nrho muab rau tib qhov chaw ntawm oxytocin nyob rau hauv koob tshuaj uas antagonize penile erection (Melis li al., 2010). Qhov tseem ceeb tshaj plaws, cov kab mob plab hnyuv txha muaj tshwm sim los ntawm kev ua kom muaj zog ntawm cov kua hluav taws xob ntxiv hauv lub ventral subiculum, uas tsuas yog cov antagonized los ntawm NMDA tus neeg pleev kiab (antagonist) (+) MK-801 ventral subiculum (Melis li al., 2010). Ua ke, cov ntsiab lus no qhia tau hais tias cov tshiab tsim muaj nitric oxide, los ntawm kev sib txuas lus ua tus tub txib intercellular, qhib cov txheej txheem glutamic acid neurotransmission rau rab yaj zuaj erection, tejzaum nws los ntawm neural efferent projections ntawm ventral subiculum mus rau lwm qhov chaw hippocampal hlwb. Nyob rau hauv txoj kab nrog cov lus no, NMDA raug txhaj rau hauv ventral subiculum induces penile erection nyob rau hauv ib lub tshuaj-raws li, thiab cov nyhuv no yog antagonized tag los ntawm kev txhaj tshuaj ua ntej mus rau tib qhov chaw ntawm (+) MK-801, tiam sis tsis yog S-methyl-thio-l-citrulline , hemoglobin los yog d (CH2) 5Tyr (Me) 2-Orn8-vasotocin (Melis li al., 2010). Raws li cov neural efferent pathways projecting rau ntxiv-hippocampal hlwb chaw activated los ntawm excitatory amino acids (ie, glutamic acid) nyob rau hauv ventral subiculum, nws yuav hais tias cov no yog glutamatergic, raws li feem ntau ntawm hippocampal efferent projections. Thaum lub sij hawm no, nws yuav tsuas pom tias cov kev tshawb fawb no hloov cov kev ua ub no ntawm mesolimbic dopaminergic neurons, uas tig kho qhov kev ua ntawm incerto-hypothalamic dopaminergic neurons nyob rau hauv paraventricular nucleus, uas ua rau kev ua kom oxytocinergic neurons mediating kho pob zeb erection li twb tau sib tham (saib saum toj no).

Ua rau lub plab nyom erection los ntawm ventral subiculum oxytocin tshwm sim ua ke nrog kev nce ntawm qhov kev sib ntxiv ntawm celluloid dopamine nyob rau hauv lub plhaub ntawm cov keeb kwm nucleus, thiab no nce, xws li rab qaum erection, abolished los ntawm d (CH2) 5Tyr (Me) 2- Orn8-vasotocin muab rau hauv ventral subiculum ua ntej oxytocin (Melis li al., 2009b). Ntxiv mus, txij li ntawm ventral subiculum oxytocin vim raug yuam erection kuj txo los ntawm (+) MK-801 txhaj rau hauv ventral tegmental cheeb tsam, tab sis tsis mus rau hauv cov nucleus accumbens (Melis li al., 2009b) thiab tshwm sim rau cov mob ntxiv glutamic acid nyob hauv cheeb tsam ventral tegmental, tab sis tsis nyob rau hauv cov nucleus accumbens, yog ob qho lus teb abolished ntawm d (CH2) 5Tyr (Me) -Orn8-vasotocin, txhaj rau hauv ventral subiculum ua ntej oxytocin (saib daim 3), nws yuav hais tias qhov activation ntawm mesolimbic dopaminergic neurons yog theem siab ntxiv rau cov kab mob glutamatergic neurotransmission hauv cheeb tsam ventral tegmental. Qhov no qhia tias glutamic acid-dopamine interaction tswj rab qaum erection tshwm sim hauv cheeb tsam ventral tegmental. Cov kev tshawb fawb ntxiv yog tsim nyog los xyuas seb tus pro-erectile efferentergenic pathways los ntawm subiculum mus rau ventral tegmental thaj tsam yog ncaj nraim los yog indirect, ie, los ntawm prefrontal cortex los yog lwm qhov chaw hauv lub hlwb (saib Melis li al., 2009b thiab cov ntaub ntawv nyob hauv). Txij thaum paraventricular nucleus tau txais glutamatergic projections los ntawm hippocampus (saib saum toj no thiab Saphier thiab Feldman, 1987), thiab glutamic acid activates paraventricular oxytocinergic neurons nrog rau cov neeg ua haujlwm rau ventral tegmental cheeb tsam (saib Argiolas thiab Melis, 2005 thiab cov lus nug nyob hauv), thiab oxytocin nyob rau hauv ventral tegmental cheeb tsam induces penile erection thiab ua rau cov kev ua ntawm mesolimbic dopaminergic neurons (saib saum toj no), nws yog kev ntxias kom xav tias paraventricular oxytocinergic neurons kuj yuav tau koom tes, tsawg kawg hauv ib feem, thaum ua kom tus mob mesolimbic dopaminergic neurons los ntawm oxytocin txhaj rau hauv ventral subiculum (saib Tshooj 4).

4. Thaum xaus lus

Cov kev tshawb xyuas rov los xyuas dua thiab pom cov kev tshawb pom thaum ntxov pom tias txiv neej nas cov oxytocin plays lub luag hauj lwm tseem ceeb hauv lub hauv paus tswj ntawm rab qaum erection nyob rau theem ntawm cov leeg paraventricular ntawm hypothalamus thiab ntawm cov leeg txha caj qaum. Nyob rau hauv kev, feem ntau rentsig txog kev tshawb fawb qhia tias oxytocin influences penile erection kuj los ntawm kev ua rau lwm lub hlwb, piv txwv li, ventral tegmental thaj tsam, lub ventral subiculum, thiab posteromedial cortical nucleus ntawm amygdala.

Nyob rau theem siab, qhov kev tshawb nrhiav tseem ceeb tshaj plaws yog qhov kev nrhiav tau ntawm tag nrho cov dopamine receptors ntawm tsev neeg D2 (D2, D3 thiab D4) nyob rau hauv lub cev ntawm lub cev ntawm oxytocinergic neurons nyob rau hauv paraventricular nucleus (thiab nyob rau hauv nucleus supraoptic thiab thaj tsam kws kho mob ua ntej) (Baskerville thiab Douglas, 2008; Baskerville li al., 2009). Qhov no ua rau muaj zog neuroanatomical kev txhawb rau qhov kev xav tias dopamine thiab dopamine receptor agonists yuav qhib tau ncaj qha oxytocinergic neurons koom rau hauv kev ua haujlwm erectile thiab projecting tsis tsuas rau cov leeg txha caj qaum xwb, tab sis kuj yuav ntxiv hypothalamic hlwb chaw. Hauv qhov no, nws tseem ceeb heev rau qhov kev tshawb nrhiav tias dopamine receptor agonist-vim raug nce siab hauv kev nrhau intracavernous yog txo los ntawm blockade ntawm oxytocinergic receptors hauv lumbo-sacral spinal qord (Baskerville li al., 2009). Xwb, txawm tias cov ntaub ntawv pov thawj no tau raug tau los ntawm cov txiv neej niam txiv lub cev, qhov kev pom zoo yuav ua rau lub koom haum ua rau lub cev tsis muaj zog ntawm qhov kev ua rau cov pob txha los ntawm tus dopamine receptor agonist induced penile erection. Hhnoos, nws tseem yuav tsum tau xav tias seb rab qau erection induced los ntawm cov stimulation ntawm dopamine receptors tam sim no nyob rau hauv oxytocinergic ntawm lub cev lub cev yog kev ua kom tiav ntawm ib hom dopamine reseptor subtype ntawm tsev neeg D2 (D2, D3 los yog D4) los sis yog hais tias cov neeg tau txais kev pab no tau ua hauj lwm hauv kev kho cov teeb meem ntawm erectile, tejzaum nws muaj ntau txoj hau kev nyob ntawm cov ntsiab lus hauv rab qau erection tshwm sim (saib Moreland li al, 2004; Enguehard-Gueiffier li al., 2006; Melis et al. 2006a, b; Löber et al., 2009; Collins et al., 2009; Depoorter li al., 2009; Baskerville li al., 2009).

Lwm qhov tseem ceeb tshiab yog tias oxytocin induces penile erection thaum txhaj tshuaj tsis tsuas rau hauv qhov chaw parabentricular los yog CA1 teb ntawm hippocampus, tab sis kuj mus rau hauv ventral tegmental, ventral subiculum, thiab posteromedial cortical nucleus ntawm amygdala. Cov kev kuaj ntawm lub hlwb tsis tau kuaj nyob rau hauv cov kev tshawb fawb ua ntej pom tias oxytocin ntau zaus mob txhaws ntswg erections ua rau cov txiv neej nas, tab sis lawv tau txais zoo li lub lumbo sacral spinal qaum oxytocinergic projections los ntawm paraventricular nucleus. Oxytocin tau pom tseeb tias muaj peev xwm ua rau mob plab hnyuv qeeb, uas tshwm sim rau hauv tus neeg laus cov txiv neej cov nqaij ntshiv thaum tsis muaj kev sib deev, xws li cov neeg uas tuaj yeem los ntawm kev nkag mus lossis cov kws kho mob tsis muaj mob (estrogen-progesterone primed) ovarianectomised poj niam kev tswj ntawm genitalia, wheninjected rau hauv paraventricular nucleus thiab CA1 teb ntawm hippocampus, tab sis tsis nyob hauv dorsal subiculum, lub lateral septum, caudate nucleus, thaj tsam medial preoptic, lub ventromedial nucleus thiab cov nucleus supraoptic (Melis et al. , 1986). Hauv cov kev tshawb fawb no, feem ntau suav thaum tus tub ntxhais tau tawm ntawm lub ntsej muag luag ntxhi los ntawm tus neeg saib xyuas uas tsis paub txog cov kev kho mob ncaj qha thaum lub sij hawm sim los yog tom qab los ntawm kev soj ntsuam cov kev sim uas tau kaw tseg rau hauv cov yeeb yaj kiab uas muaj yees duab yees duab. Txhua rab qau erection rov hla rau 0.5-1 min thiab feem ntau yog nrog cov tub rog hnav thiab / los yog ntawm cov quav. Tsis muaj kev sim ntau dua hauv cov nas tsuag kom pom tseeb tias qhov kev sib deev ntawm kev sib deev, hnub nyoog los yog yog tias cov nas tsuag tau muab faib rau cov neeg qis los sis siab rau cov teeb meem ntawm oxytocin uas raug txhaj rau hauv cov cheeb tsam hauv hlwb. Qhov no kuj siv rau feem ntau ntawm cov kev tshawb fawb ntawm cov nyom pro-erectile ntawm lwm cov neuropeptides thiab cov tshuaj uas ua rau mob plab hnyuv erections, nrog rau dopamine agonists, excitatory amino acids, ACTH-MSH, hexarelin thiab VGF peptides. Txawm li cas los, cov nyhuv pro-erectile ntawm cov keeb no tau raug dua los ntawm kev siv cov tshuaj tua kab mob, uas txiav txim xyuas qhov tshwm sim ntawm rab qau erection los ntawm kev nce hauv kev ceev nrig uas tshwm sim los yog tom qab kev siv cov kev sib txuas ntawm cov kev sib txawv, xws li, systemically, intracerebroventricularly los yog ncaj qha mus rau hauv lub hlwb lub hlwb, tom qab cog ntawm lub siab microtransducer ncaj qha mus rau hauv lub tuam txhab cavernous (saib Bernabè li al., 1999). Hauv cheeb tsam ventral tegmental, ventral subiculum thiab posteromedial nucleus ntawm amygdala kuj oxytocin induces penile erection los ntawm cov pa oxytocinergic receptors. Qhov no ua rau qhov activation ntawm mesolimbic dopaminergic neurons originating nyob rau hauv ventral tegmental cheeb tsam thiab projecting rau lub plhaub ntawm lub keeb tawm accumbens, raws li ntsuas los ntawm kev ntxiv hauv cell-dopamine concentration hauv lub dialysate uas tau los ntawm lub plhaub ntawm cov pa nucleus accumbens thiab los ntawm qhov txo ntawm cov lus teb rau lo lus yuam los ntawm peptide txhaj rau hauv cov nrawm qaum-qhov chaw ntxiv, nrhiav tau tom qab qhov blockage ntawm dopaminergic receptors nyob rau hauv nucleus accumbens (saib hauv qab). Raws li cov tswv yim tsim los ntawm kev ua kom oxytocinergic receptors nyob rau hauv cov cheeb tsam ntawm lub hlwb, uas ua rau lub activation ntawm mesolimbic dopaminergic neurons thiab rau rab yaj zuaj erection, qhov zoo tshaj plaws clarified yog cov tshwm sim nyob rau hauv lub caudal ventral tegmental cheeb tsam. Xwb, ntawm no cov tshuaj pharmacological thiab immuno-fluorescence tau qhia tau hais tias oxytocin paj thaiv qhov kawg impinge ntawm lub cev lub cev ntawm dopaminergic neurons rau lub plhaub ntawm cov nucleus accumbens (Melis et al., 2007, 2009a; Succu et al., 2008). Muaj ntau ntawm cov neurons no muaj nitrite oxide synthase thiab nyob hauv guanylate cyclase. Lub stimulation ntawm oxytocinergic receptors nyob rau hauv lub cev ntawm lub cev ntawm cov dopaminergic neurons ua rau activation ntawm nitric oxide synthase txoj hau kev nce nitric oxide ntau lawm. Nitric oxide nyeg pib ua guanylate cyclase, ua qhov nce ntawm qhov kev sib hloov ntawm cyclic GMP, uas ua rau cov neeg ua haujlwm ntawm mesolimbic dopaminergic neurons thiab rau kev tso tawm ntawm dopamine nyob rau hauv lub nucleus accumbens, raws li ntsuas los ntawm kev nce ntxiv hauv cellular dopamine hauv lub dialysate los ntawm nucleus accumbens tau txais los ntawm intra-cerebral microdialysis (Succu et al., 2008 ). Dopamine tso tawm rau hauv lub nucleus accumbens nyob rau hauv tig activates neural txoj kev ua rau rab qau erection. Qhov no yog kev txhawb los ntawm kev muaj peev xwm ntawm dopamine receptor antagonists haloperidol thiab / lossis cis-flupentixol txhaj rau hauv lub nucleus accumbens los txo cov ventral tegmental tsam oxytocin huas penile erection (Succu li al., 2008). Ib qho ntawm txoj hauv kev pro-erectile zoo li qhib cov thev naus laus zis-hypothalamic dopaminergic neurons, tshwj xeeb tshaj yog cov uas tsim kom muaj lub cev ntawm cov kab mob ntawm cov kab mob paraventricular oxytocinergic neurons. Xwb oxytocin txhaj rau hauv caudal ventral tegmental thaj tsub ntxiv cov tshuaj extracellular dopamine tsis tsuas yog nyob rau hauv cov nucleus accumbens tab sis kuj nyob rau hauv paraventricular nucleus, thiab cov blockage ntawm dopamine receptors nyob rau hauv paraventricular nucleus thiaj li ventral tegmental tsam oxytocin huas penile erection (Succu li al. , 2007, 2008; Melis li al., 2007, 2009a). Lub hav zoov ntawm cov nucleus accumbens dopamine-paraventricular dopamine-paraventricular oxytocin-ventral tegmental tsam oxytocin-dopamine links tseem pom tias muaj peev xwm ntawm ib qho kev tiv thaiv ntawm apomorphine thiab D4 receptor agonist PD 168077 txhaj rau hauv paraventricular nucleus kom ntxiv cov cellular dopamine hauv lub plhaub ntawm cov keeb kwm nucleus (Succu et al., 2007) uas yog tshem tawm ntawm d (CH2) 5Tyr (Me) -Orn8-vasotocin muab rau hauv ventral tegmental thaj tsam (Melis thiab lwm tus, 2009a, saib hauv qab no). Txawm li cas los xij, kev ua hauj lwm ntxiv yog tsim nyog los txheeb xyuas cov neural pathways uas txuas cov nucleus accumbens mus rau incerto-hypothalamic dopaminergic system.

Lub mechanism uas oxytocin induces penile erection thiab activates mesolimbic dopaminergic neurons thaum txhaj rau hauv ventral subiculum los yog hauv posteromedial nucleus ntawm lub amygdala yog tsuas yog to taub thaum lub caij. Hauv cov cheeb tsam no, oxytocin activates nws tus kheej receptors uas ua rau kom cov activation ntawm nitric oxide-synthase, ua li cov nitric oxide ntau lawm. Nitric oxide nyeg pib qhib tsis tau paub tias muaj qhov zoo li cas, uas yog qhov nce ntawm glutamatergic neurotransmission hauv cheeb tsam ventral tegmental. Glutamic acid ces stimulates mesolimbic dopaminergic neurons txoj hau kev rab qau erection. Qhov kev pom zoo no yog txhawb los ntawm kev muaj peev xwm ntawm oxytocin txhaj rau hauv ventral subiculum kom ntxiv cov cellular glutamic acid hauv ventral tegmental cheeb tsam (Fig. 3), thiab ntawm NMDA tus neeg mob reseptor antagonist (+) MK-801 txhaj rau hauv ventral tegmental cheeb tsam, tab sis tsis nyob rau hauv cov nucleus accumbens, kom txo tau cov pob txha txhav los ntawm oxytocin txhaj rau hauv ventral subiculum los yog hauv posteromedial nucleus ntawm cov amygdala (Melis li al., 2009b). Thaum lub sij hawm, ntau cov ntsiab lus muaj rau lub ventral subiculum oxytocin huas penile erection. Ntawm no oxytocin huas penile erection kheej rau qhov ua kom muaj oxytocinergic receptors nyob hauv lub cev ntawm nitric oxide-synthase-muaj neurons. Qhov no ua rau muaj qoob zus ntxiv ntawm nitric oxide, uas ua rau glutamatergic neurotransmission los ntawm kev ua ib tug tub xa xov xwm sib txuas lus nrog ib txoj haujlwm zoo li uas tau piav rau cov neeg ua haujlwm ntev (saib Snyder, 1992; Southam thiab Garthwaite, 1993; Schuman thiab Madison, 2004) . Nyob rau hauv cov kab mob nrog rau cov kab mob no ua rau cov neeg mob plab hnyuv taum ntawm cov tshuaj hu ua NMDA, induces penile erection. Glutamic acid nyob rau hauv lem activates neural efferent projections, uas ua rau cov activation ntawm mesolimbic dopaminergic neurons hauv cheeb tsam ventral tegmental, raws li saum toj no qhia. Yog hais tias cov mechanisms no kuj ua haujlwm nyob rau hauv cov posteromedial nucleus ntawm amygdala tsis paub tam sim no. Ntxiv mus, cov kev tshawb fawb ntxiv yuav tsum muaj pov thawj tias (1) oxytocinergic paj thaiv qhov xaus thiab cov neeg tawm suab hauv ventral subiculum thiab cov posteromedial nucleus ntawm amygdala yog nyob hauv lub cev ntawm lub cev ntawm cov neurons muaj nitric oxide-synthase, (2) yog tias cov neurons yog qhov kawg nyob rau hauv kev tswj ntawm excitatory amino acid (glutamatergic) synapses thiab (3) los txheeb xyuas cov phiajcim system activated los ntawm nitric oxide. Hauv no regard, nws yog noteworthy tias lub peev xwm ntawm oxytocin kom nitric oxide-synthase kev ua hauv lub cev ntawm dopaminergic neurons hauv cov caudal ventral tegmental thiab tseem tsis paub hais tias neurons hauv ventral subiculum thiab posteromedial nucleus ntawm amygdala, qhov kev muaj peev xwm ntawm oxytocin mus qhib nitrich oxide-synthase nyob rau hauv lub cev ntawm lub cev ntawm oxytocinergic neurons nyob rau hauv paraventricular nucleus (Melis li al., 1997). Txawm li cas los xij, thaum nyob hauv ventral tegmental thaj tsam ntau ntxiv ntawm nitric oxide nyob rau hauv lub cev ntawm dopaminergic neurons ua rau cov activation ntawm cov neurons los activating guanylate cyclase thiab nce cyclic GMP, qhov no tsis tshwm sim hauv cov keeb kwm parabentricular nucleus. Raws li, 8-bromo-cyclic GMP txhaj rau hauv paraventricular nucleus tsis induce penile erection, thaum nws ua li ntawd thaum muab tso rau hauv thaj tsam ventral tegmental. Lwm qhov chaw sib txawv ntawm qhov sib txawv ntawm cov pa nitric oxidecyclic GMP ces tau muab kev koom tes rau theem siab ntawm qhov kev ua kom muaj zog ntawm oxytocinergic neurons nruab nrab ntawm cov tshuaj tua hluav taws xob los ntawm exogenous nitric oxide (Melis thiab Argiolas, 1995b; Melis et al., 1997) . 1). Ntawm qhov tod tes, cyclic GMP hauv ventral tegmental tsam nkawd ua si tseem muaj lub luag haujlwm tseem ceeb hauv txoj kev ua ntawm mesolimbic dopaminergic neurons thiab nce nyob rau hauv ntxiv-cellular dopamine tshwm sim nyob rau hauv lub dialysate tau los ntawm lub plhaub ntawm nucleus accumbens ntawm txiv neej nas xaiv rau qhov qhia lossis tsis qhia cov tshuaj tua tsis tau tus kheej thaum uas muab tso rau hauv lub xub ntiag ntawm ovariectomized receptive (estrogen + progesterone kho) tus poj niam nas. Nyob rau hauv cov kev sim no, cov txiv neej nas uas pom tias tsis muaj kev sib raug zoo ntawm cov pob qij txha, muaj qhov nce ntxiv ntawm tus xov tooj ntawm dopamine nyob raws li qhov kev xav, thiab qhov nce no ntxiv zuj zus ntxiv, txawm tias tsuas yog txuam nrog, los ntawm phosphodiesterase inhibitors rau hauv caudal ventral tegmental (Sanna et al., 2009).

Lub peev xwm ntawm oxytocin txhaj rau hauv ventral tegmental cheeb tsam, nyob rau hauv ventral subiculum thiab nyob rau hauv posteromedial cortical nucleus ntawm amygdala, ua ke nrog cov dopamine agonists txhaj rau hauv paraventricular nucleus, kom induce penile erection thiab qhib mesolimbic dopaminergic neurons deserves ib txhia saib . Ua ntej, cov tswv yim zoo li cov uas tau hais los saum toj no yuav tsum ua hauj lwm thaum cov pob txha txhaws hauv lub cev muaj zog, xws li thaum lub sij hawm copulation (thaum nyob rau hauv copula penile erections tshwm sim) los yog thaum lub sij hawm siv tshuaj tua tsis tau. Cov kab mob no yog pheromone-mediated penile erections indistinguishable los ntawm cov raug vim cov tshuaj yeeb los yog oxytocin, uas tshwm sim thaum muaj kev sib deev hwj chim txiv neej raug muab tso rau hauv lub xub ntiag ntawm cov tshuaj tsis tuaj yeem (ovariectomized estrogen + progesterone primed) tus poj niam tus txiv neej thiab pom tau tias yog qhov ntsuas ntawm kev sib deev arousal (Sachs, 1997, 2007). Qhov tseeb tiag, txawm tias cov ntsiab lus no tsis pom tias oxytocin nyob rau hauv cov cheeb tsam no plays lub luag haujlwm nyob rau hauv kev mob plab zom zaws los yog tom qab siv tshuaj tua kab mob, lawv ntxiv zog ntxiv rau cov kev tshawb pom thaum ntxov qhia tias cov cheeb tsam ntawm lub hlwb raug rau cov neeg qhov chaw oxytocin uas muab cov kev ua haujlwm nce tsis yog tsuas yog mob txhaws qa lub plawv (erectile erections) tom qab pom kev siv tshuaj yaj yeeb, tab sis kuj ua kom cov txiv neej (thiab poj niam) tus cwj pwm kev sib deev (saib Argiolas thiab Melis, 2004 thiab cov lus qhia nyob hauv). Raws li, oxytocin concentration tsub kom nyob rau hauv hippocampus ntawm cov txiv neej nas kho nrog ib tug pro-erectile koob ntawm apomorphine, ib classical dopamine agonist (Melis li al., 1990) thiab d (CH2) 5Tyr (Me) -Orn8-vasotocin, uas thaiv oxytocin receptors, tsis tshua muaj txiaj ntsim zoo rau kev ua rau tus cwj pwm tsis zoo (Argiolas thiab al., 1987a), tiam sis tseem yog cov nyhuv ntawm apomorphine rau txiv neej tus cwj pwm (Argiolas thiab al., 1987b) hauv cov nas zog ntawm kev sib deev, thaum lub sij hawm nyob rau hauv copula penile erection tshwm sim. D (CH2) 5Tyr (Me) -Orn8-vasotocin kuj tseem ceeb heev rau kev txo cov ntsiab lus tsis pub muaj kev sib deev hauv cov txiv neej sib deev uas muaj hwj chim, thaum muab cov nanogram tso rau hauv cov pos hniav, tiam sis tsis yog hauv PVN (Melis thiab lwm tus, 1999a).

Thib ob, mesolimbic dopaminergic neurons ua si lub luag haujlwm tseem ceeb hauv kev txhawb zog thiab kev txhawb zog ntawm kev txhawb zog, xws li zaub mov, dej thiab kev sib deev (Fibiger thiab Phillips, 1988; Wise thiab Rompre, 1989; Everitt, 1990). Hauv particular, dopamine tso tawm los ntawm cov neurons no yog xav kom sib hais txog kev sib txuas lus ntawm kev ua kom muaj zog ntawm lub cev ua kom muaj lub hom phiaj coj tus cwj pwm, piv txwv tias yog kev sib deev, kev nrhiav kev sib deev thiab kev sib daj sib deev kom ncav cuag lub txiaj ntsim thiab kev txaus siab (Goto thiab Hlub, 2005). Raws li, kev sib txuas ntawm cov pob txha yuav ua rau nyob rau hauv kev sib txuas ntawm cov neeg lim ntshav ntawm cov nucleus ntawm cov naj hla tus txiv neej thaum lub sij hawm kis tau tus kabmob ua tsis taus pa ovarianectomized estrogens + progesterone-primed receptive female rat, thiab xws li nce siab dua thaum tus txiv neej tau raug tsom mus nrog tus poj niam receptive (Pfaus thiab Everitt, 1995).

Qhov thib peb, qhov kev tshwm sim tam sim no txhawb qhov kev pom zoo tias lub thev neural txuas rau qhov kev sib tshuam ntawm cov neural nrog lub ventral tegmental thaj tsam ncaj nraim los yog tsis ncaj (ntawm lub ventral subiculum thiab / los yog posteromedial cortical nucleus ntawm lub amygdala) thiab cov nucleus accumbens, thiab los ntawm no mus txog txoj kev rov tuaj dua mus rau qhov chaw parabentricular nucleus tswj cov kev ua ntawm oxytocinergic neurons projecting rau tus txha nqaj qaum mediating penile erection thiab ntawm oxytocinergic neurons projecting ventral tegmental, ventral subiculum thiab posteromedial cortical nucleus ntawm amygdala, modulating li no kev ua haujlwm ntawm mesolimbic dopaminergic neurons (daim duab 4). Txoj kev ua neural Circuit Court tej zaum yuav ua si hauv kev koom ua ke ntawm kev ua si hauv neural cuam tshuam rau kev tswj ntawm cov khoom noj khoom haus (erectile-ejaculatory) thiab kev cia siab (motivational thiab nqi zog) ntawm cov poj niam txiv neej tus cwj pwm nyob rau hauv physiological contexts. Qhov tseeb, dopamine ntxiv rau hauv nucleus accumbens (Pfaus thiab Everitt, 1995) thiab nyob rau hauv kev sib deev parisentricular nucleus ntawm cov txiv neej muaj zog cov nas zog thaum muaj kev cuam tshuam rau ib tug neeg tsis tuaj yeem tso tus poj niam nas, thaum tsis muaj kev sib txuas lus, thiab txawm ntau tshaj thaum kev pub luam, xws li, thaum muaj kev sib deev hauv cov pob txha qaij (Melis li al., 2003). Yog li, txawm tias cov kev tshawb fawb ntxiv yuav tsum tau qhia meej txog lub luag hauj lwm ntawm cov oxytocin hauv cov ventral tegmental, lub ventral subiculum thiab cov amygdala thaum lub cev tsis muaj kev sib deev thiab kev coj tus cwj pwm, nws yuav tsim nyog xav tias qhov teeb meem loj no nees zoo li, Kev sib txuas lus ntawm kev sib deev, tib lub sij hawm kuj tseem yuav tau qhib lub mesolimbic dopaminergic system muab lub neural substrate rau piav qhia txog cov khoom txiaj ntsim ntawm kev sib deev (Everitt, 1990; Pfaus thiab Everitt, 1995). Nyob rau hauv no regard, nws yog noteworthy tias lub mesolimbic dopaminergic system activated los ntawm oxytocin txhaj rau hauv ventral tegmental tsam yog tib activated los ntawm cov tshuaj ntawm kev tsim txom xws li opiates, cannabinoids, amphetamine, yeeb thiab haus cawv (Tanda thiab al., 1997), thiab tias oxytocin tau pom muaj peev xwm txo tau kev ua siab ntev thiab kev vam meej rau yeeb dawb, morphine, cawv thiab cannabinoids (Kovacs li al., 1998; Cui li al., 2001). Nyob rau hauv xaus, nws zoo li hais tias oxytocin tso tawm tsis tsuas yog nyob rau hauv ventral tegmental cheeb tsam, tab sis kuj nyob rau hauv lub ventral subiculum thiab posteromedial cortical nucleus ntawm amygdala, muaj peev xwm activate mesolimbic dopaminergic neurons, uas tej zaum yuav koom tes nyob rau hauv lub zog thiab nqi zog ntawm kev sib deev kev ua si . Kev pib ntawm mesolimbic dopaminergic neurons tuaj yeem ncaj qha, los ntawm oxytocinergic receptors nyob rau hauv lub cev ntawm mesolimbic dopaminergic neurons, los yog indirect los ntawm kev ua kom muaj glutamic acid neurotransmission hauv ventral tegmental.

Dopamine tso tawm rau hauv cov keeb kwm plhaub hauv plhaub tus plhaub ntim rau qhov kev ua si ntawm qhov incerto-hypothalamic dopaminergic neurons nyob rau hauv paraventricular nucleus uas ua rau cov pob txha (tsis pub ua rau ntawm oxytocinergic neurons projecting rau tus txha caj qaum), los yog kev sib deev kev xav thiab nqi zog (ntawm kev ua kom oxytocinergic neurons projecting mus rau ventral tegmental cheeb tsam, lub ventral subiculum los yog posteromedial cortical nucleus ntawm amygdala). Txij li thaum dopamine kuj tso tawm hauv cov keeb kwm ntawm cov nucleus accumbens thiab hauv qhov chaw parabentricular nucleus thaum cov pob txha erection tshwm sim nyob rau hauv kev siv lub cev (piv txwv li, kev sib txuas lus tsis muaj leej twg thiab copulation) (Succu thiab al., 2007; Melis et al., 2003, 2007), nws yog tej zaum cov central oxytocinergic neurons koom hauv neural circuits mediating kev sib cuam tshuam ntawm cov mesolimbic thiab incerto-hypothalamic dopaminergic system. Cov neural circuits no yuav ua rau lub luag hauj lwm tsis yog nyob hauv lub sijhawm ua kom muaj kev sib daj sib deev (piv txwv li, kev tsim menyuam thiab kev sib txuas lus), tiam sis tseem muaj kev sib deev kev sib deev, kev sib deev kev sib deev thiab kev sib deev.

Daim duab 4.

Schematic sawv cev ntawm qhov hypothetical neural circuitry uas muaj oxytocin cuam tshuam rau kev sib deev kev txhawb, kev qhuas thiab kev sib deev ua, raws li tau pom los ntawm cov ntsiab lus ntawm tshooj lus no thiab cov lus qhia dhau los. Oxytocinergic neurons pib tawm ntawm cov leeg pob txha thiab ua haujlwm rau cov leeg txha nqaj qaum thaum pib ua rau dopamine thiab glutamic acid (tab sis kuj los ntawm lwm cov neurotransmitters thiab / los yog neuropeptides), pab txhawb kev siv tshuaj tiv thaiv thiab kev sib deev los ntawm activating oxytocinergic neurons projecting rau tus txha caj qaum. Dopamine thiab glutamic acid (tab sis kuj neurotransmitters thiab neuropeptides) nyob rau hauv paraventricular nucleus kuj activates oxytocinergic neurons projecting rau ventral tegmental, li no activating mesolimbic dopaminergic neurons projecting rau cov nucleus accumbens, modulating kev sib deev motivation thiab nqi zog. Dopamine tso tawm rau hauv cov nucleus accumbens (NAs) qhib qhov tseem tsis pom kev neural pathways, uas ua rau cov kev ua ntawm incerto-hypothalamic dopaminergic neurons (pib hauv A13-A14 pawg Dahlstrom thiab Fuxe) impingingamongothers ntawm oxytocinergic neurons, nrog rau cov uas tsim tus txha caj qaum, ua rau rab qau erection. Cov circuitry no kuj yuav tsum tau siv los ntawm oxytocin txhaj tshuaj nkaus xwb tsis yog hauv cov caudal ventral tegmental, tab sis kuj nyob hauv ventral subiculum thiab nyob rau hauv amygdala, uas tau txais oxytocinergic kev txuag los ntawm paraventricular nucleus, tejzaum nws los ntawm kev ncaj qha lossis tsis ncaj qha glutamatergic efferent mus rau ventral tegmental cheeb tsam, ua rau cov kev taw qhia ntawm ob qho kev sib deev kev cai thiab kev siv tshuaj tiv thaiv penile. Thaum kawg, cov xov tooj cua saum toj no kuj yuav tau qhib lub zog ntawm kev sib deev thiab pheromones, vim cov celluloid dopamine thiab glutamic acid nce nyob rau hauv qhov chaw parabentricular nucleus (thiab thaj tsam thaj tsam ntawm thaj tsam) thaum lub sij hawm pheromone-mediated noncontact erections thiab copulation (rau cov references tsim nyog saib Cov npe chiv keeb).

Kev Pom Zoo Cov hauj lwm no tau txais kev pab los ntawm kev pab nyiaj los ntawm Italian Ministry of the University thiab tshawb xyuas txog AA thiab MRM

References

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