Uhlolo. Ulawulo oluphambili lwe-penile yokwakhiwa: Ukubuya kwakhona kwendima ye-oxytocin kunye nokusebenzisana kwayo kunye ne-dopamine kunye ne-glutamic acid kwiimvumi zamadoda (2011)

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

Melis MR¹, Argiolas A.

KWI-ABSTRACT

I-Oxytocin yiyona nto inducer enamandla yokwakhiwa kwe-penile xa ijojowe kwi-system central nervous system. Kwiingqungqingi zendoda, indawo yengqondo eyona nto ingabonakaliyo kwimiphumo ye-pro-erectile ye-oxytocin yiyona nucleus eplastiki ye hypothalamus. Le nucleus kunye nemimandla engqongileyo iqulethe iisilini zee-oxytocinergic neurons ezixhomekeke kwimimandla yengqondo kunye ne-spinal cord. Olu hlalutyo lubonisa ukuba i-oxytocin yenza ukuba i-penile erection ibe nayo xa ijojowe kwezinye zezo ndawo (umzekelo, indawo ye-ventral tegmental, i-ventral subiculum ye-hippocampus, i-posteromedial cortical nucleus ye-amygdala kunye ne-thoraco-lumbar cord). Izifundo ze-Microinjection kunye ne-microdialysis ye-intra-cerebral kunye nezifundo eziphindwe kabini ze-immunofluorescence zibonisa ukuba i-oxytocin kule mimandla iyasebenza ngokuthe ngqo okanye ngokungathanga ngqo (ikakhulukazi nge-glutamic acid) i-mesolimbic dopaminergic neurons. I-Dopamine ekhutshwe kwi-nucleus i-accumbens ivulela i-neural pathways ekhokelela ekusebenziseni i-incerto-hypothalamic ne-dopaminergic neurons kwi-nucleus ephambili. Oku kusebenze kuphela i-oxytocinergic neurons eyenza umgca we-spinal kunye nokudibanisa i-penile erection, kodwa nabo baxhomekeke kwimimandla engaphezulu ye-hypothalamic, ukucwangcisa ngokuthe ngqo okanye ngokungathanga ngqo (ngokusebenzisa i-glutamic acid) umsebenzi we-mesolimbic neoponergic neurons olawula ukukhuthazwa kunye nomvuzo. Ezi zinto zihamba ngeendlela ezihamba phambili zingenza isiphaluka esichukumisayo, esenza indima kungekhona kuphela kwisigaba sokusetyenziswa kwesondo (umsebenzi we-erectile kunye nokuxubusha), kodwa nakwizinto ezikhuthazayo nezivuzayo zesigaba esilindelekileyo sokuziphatha ngokwesondo.

1.Ingxelo

Ukulungiswa kwePenile yindlela yokuziphatha ngokwesini edlala indima ephambili ekuzaliseni izilwanyana ezinjengezilwanyana, kwaye ezinokuthi ziphinde zigcinwe kwiimeko ezahlukeneyo kwezo zinto zihambelana nokuzaliswa. Kuxhomekeka kwimeko apho kwenzeka penile ukwakhiwa, ezahlukeneyo kwenethiwekhi engundoqo kunye neuropathy kunye / okanye iindlela humoral inxaxheba kumgaqo wayo (bona Meisel kunye Sachs, 1994; Argiolas kunye Melis, 1995, 2004, 2005; Sachs, 2000, 2007; McKenna, 2000; Giuliano kunye neRampin, 2000, 2004; Andersson, 2001; uMelis no-Argiolas, 1995a, 2003; Hull et al., 2002). Phakathi kwama-neurotransmitters kunye nama-neuropeptide alawula i-penile erection, eyaziwayo kakhulu i-dopamine, i-serotonin, i-amino acidatory, i-nitric oxide, i-adrenocorticotropin, i-oxytocin ne-opioid peptides. Bangakwazi ukuququzelela okanye ukuvimbela ukulungiswa kweepenile ngokusebenza kwiindawo ezininzi zeengqondo, oko kukuthi, indawo yangaphambili yomda, i-nucleus eplastiki ye hypothalamus, indawo ye-ventral, i-hippocampus, i-amygdala, i-nucleus yebhedi ye-stria terminalis, i-nucleus accumbens, i-medulla oblongata kunye nentambo yomthambo (Table 1) (jonga Meisel kunye Sachs, 1994; Witt kunye Insel, 1994; Stancampiano et al, 1994;. Argiolas kunye Melis, 1995, 2005; Argiolas, 1999; Bancila et al, 2002;. Giuliano kunye Rampin, 2000, McKenna, 2000; Andersson, 2001; Hull et al., 2002; Coolen et al., 2004).

Yioxytocin, lo peptide neurohypophyseal eyaziwa kakuhle indima yalo kwamadlala kwi zisanyisa kunye parturition, ekhona kwamabhinqa namadoda, kungekuphela luvo kunye namaqumrhu iseli ibekwe kwi paraventricular kunye supraoptic eziba le ngxenye ejonge ukuya neurohypophysis, kodwa iiseli zemithambo-luvo nibonise ukususela kwi-nucleus yeparagraphics kunye nezakhiwo ezizungezile kwiindawo zengqondo ze-extrahypothalamic (oko kukuthi, i-septum, indawo ye-ventral, i-hippocampus, i-amygdala, i-medulla oblongata kunye nentambo yomthambo). Ezi zi-neuron zicingelwa ukuba zibandakanyeka kwimisebenzi emininzi ephakathi, njengememori, ukufunda, ukusebenzisana kunye nokuziphatha kwezesondo, kuquka ukulungiswa kwe-penile kunye nokuziphatha okuxilisayo (bona i-Buijs, i1978; i-Sofroniew, i-1983; iArgiolas neGessa, i-1991; i-Pedersen et al , I-1992; iCarter, i-1992; i-Wagner ne-Clemens, i-1993; i-Ivell ne-Russel, i-1995; iCarter et al., I-1997; i-Tang et al., I-1998; i-Veronneau-Longueville et al., I-1999). Eneneni, yioxytocin lula umsebenzi erectile kunye nokuziphatha ngokwezesondo eyindoda iimpuku, iimpuku, imivundla neemfene (bona Argiolas kunye Gessa, 1991; Carter, 1992;. Pedersen et al, 1992; Argiolas kunye Melis, 1995, 2004; Argiolas, 1999). Oku kunokwenzeka nakubantu, ekubeni i-plasma oxytocin yonyuswa ngesistim sezesondo, ngakumbi kwi-ejaculation (i-Carmichael et al., I-1987; i-Murphy et al., I-1987) kunye nokusetyenziswa kwebele kunye ne-genitalia, edlalwa ngexesha lezesondo isondo (Tindall, 1974).

I-oxytocin yendlela yokuziphatha ngokwesini yabonisa okokuqala ukuba amandla okwenza i-oxytocin i-intravenous oxtocin iyancipha ukunciphisa i-latency ukuya ekuthomeni kokuqala kunye nokukhawuleza ukuxhatshazwa ngokwesondo ngokobulili besilisa obudibeneyo kunye nabafazi abathobelayo (uMelin no-Kihlstrom, i-1963). Nangona kunjalo, iziphumo zesini zesimo se-oxytocin zaziqatshelwa ngokuqinisekileyo kuphela kwiminyaka engama-80. I-Oxytocin eyinikwe ngokuyinhloko kwixabiso le-nanogram yafunyanwa yakwazi ukunyusa i-penile erection (Argiolas et al., 1985, 1986) kunye nokuphucula indlela yokuziphatha (Arletti et al., 1985) kwiinkokhwe zamadoda, kunye nokwandisa i-lordosis kwiinkikazi zamabhinqa (Arletti kunye ne-Bertolini, i-1985; iCaldwell et al., i-1986), ngokubonakalayo ngokubambela i-oxytocinergic receptors (i-Argiolas no-Melis, i-1995, i-2004; i-Argiolas, i-1999; i-Melis ne-Argiolas, i-2003 kunye neenkcukacha zayo). I-Oxytocin iphucula ukuziphatha ngokwesondo kungekhona kuphela kwiigundane zesondo (i-Arletti et al., I-1985) kodwa kunye nasezintwini ezindala (Arletti et al., 1990), kwaye ziphezulu, kodwa zingekho ngaphantsi, iinduna ze-squirrel (i-Winslow neInsel , 1991).

Impembelelo e-erectile ye-oxytocin yixhomekeke kwi-testosterone, njengoko ipheliswa yi-hypophysectomy kunye ne-castration, kwaye ibuyiselwe ngokuxhaswa nge testosterone okanye i-metabolites, i-estradiol kunye ne-5_-dihydro-testosterone kunye kunye (Melis et al., 1994a). Indawo ephosakeleyo yengqondo yokufakelwa kwe-penile yokwakhiwa yi-oxytocin yi-nucleus eplastiki ye hypothalamus (i-Melis et al., 1986), apho zonke iziqulatho ze-oxytocinergic ezivela kuzo zonke i-oxytocinergic (see ngasentla). Apha, i-oxytocin yafunyanwa ukuba ikwazi ukunyusa i-penile yokwakhiwa (kunye nokwehla) xa injected kwii-dose ziphantsi njenge-3 pmol (bona iCandelo 2.1 ngezantsi). Yioxytocin kwezi- penile ukwakhiwa kwakhona xa lesitofu bilaterally waya CA1 entsimini Hippocampus, kodwa hayi kwi subiculum amanakani (jonga kwiCandelo 2.3 ngezantsi), ekudibaneni osecaleni, ngumongo caudate, indawo medial preoptic, ngumongo ventromedial le ngxenye kunye nucleus (Melis et al., 1986). Ngokuphathelele indlela eyenziwa ngayo i-oxytocin kwi-nucleus yipalasari ukuba inokushukumisa le mpendulo yesondo, uphando oluninzi lubonisa ukuba i-oxytocin ivuselela i-neurons yayo. Ngokuhambelanayo nale ngcamango, ukusebenzisana ngokwesondo kuya kwandisa i-FOS, imveliso yemfuza ye-gene yangaphambili ye-gene c-fos kwi-neuron ye-oxytocinergic ehamba phambili eyenza i-spinal cord, echaphazelekayo ekulawulweni kwe-penile erection (bona iWitt neInsel, i-1994 kunye neenkcukacha apho), kunye nokungabikho kwesondo (umz., ukungakwazi komlingani omdala ukuba ulandele nge-ovariectomized estrogen-progesteroneprimed female receptive) kuye kwadibaniswa kwindoda yesilisa kunye namazinga aphantsi e-oxytocin mRNA kwi-nucleus eplastiki ye hypothalamus (Arletti et al., 1997).

Ingaba i-oxytocin ithonya isigaba esilindelekileyo okanye isigaba sokugqiba sendlela yokuziphatha ngokwesondo akucaci okwangoku. Njengoko i-oxytocin yenza ukuba i-penile erection ibe nempembelelo ephezulu ye-oxytocin ekuziphatheni kwe-copulatory, ukuncipha kwithuba elingaphambili lokuhamba ngeenkwenkwezi (Arletti et al., 1985), kunengqiqo ukucinga ukuba i-peptide iphucula ukusebenza kwezesondo. Nangona kunjalo, njenge-oxytocin iphinda ikhulise intsebenziswano yezobudlelwane bezocansi (bona i-Pedersen et al., I-1992; iCarter et al., I-1997; i-Ivell kunye neRussel, i-1995) kunye ne-oxytocin receptor antagonists zithintela ukungahambisani nokungqinelani (Melis et al., 1999a), kuthathwa njengengqekembe yokuvusa isondo (bona iiSachs, 1997, 2000, 2007; i-1998, i-1999, i-XNUMXb kunye neenkcukacha zayo), inxaxheba enokwenzeka ye-oxytocin ekuvukeleni ngokwesini kunye nesishukumiso soxhatshazo.

Olu hlalutyo lufingqa iimpcazo ezipapashwe kwaye ezingashicilelwa kwezifundo zangoku, ezibonisa ukuba i-oxytocin inciphisa i-penile yokwakhiwa kungekhona kuphela xa ijoyiweyo kwinucleus yecycleusmus ye-hypothalamus, kodwa nakwezinye iindawo ezinengqondo ezingaphezulu kwe-hypothalamic, ezifana ne-ventral tegmental (Melis et al., 2007, 2009a; Succu et al., 2008), ti-subiculum yangaphakathi ye-hippocampus kunye ne-nucleus yangemva kwe-amygdala (UMelis et al., 2009b, 2010), ezibalulekileyo ezibalulekileyo zeenkqubo zomlenze kwaye bacingelwa ukuba badlale indima ebalulekileyo kwimpembelelo kunye neenkqubo zokuvuza. Ezi zifundo zityhila ukuba i-oxytocin ithatha inxaxheba kwizijikelezo ze-neural, ezibandakanya ezinye i-neurotransmitters, ezifana ne-dopamine kunye ne-glutamic acid, kunye nezinye iindawo zengqondo ngaphandle kwe-nucleus epalasitiki, umzekelo, indawo ye-ventral tegmental, i-nucleus accumbens, i-hippocampus kunye neendawo eziza kuba zichongiwe. Ezi zijikelezo ziyakunxibelelanisa intsebenziswano phakathi kwe-mesolimbic kunye ne-incerto-hypothalamic dopaminergic system, kwaye idlale indima kungekhona kuphela kwisigaba sokuphela kwesenzo sokuziphatha ngokwesini (umz. ukuvusa, ngoko ke unikezela nge-neural substrate ukuchaza izinto ezikhuthazayo nezivuzayo zesenzo socansi.

2. I-Oxytocin ithonya i-penile erection ngokusebenza kwiindawo ezahlukeneyo zobuchopho

2.1. I-nucleus eplastiki ye hypothalamus

Njengoko kukhankanywe apha ngentla yesikhombisi se-hypothalamus ngokukhawuleza kwachongwa njengendawo yengqondo eyona nto ibuhlungu kakhulu kwi-pro-erectile effect ye-oxytocin. Xa injected unilaterally kule nucleus, i-oxytocin yafunyanwa isebenzayo kwiiyithithi eziphantsi njenge3 ng (3 pmol) (Melis et al., 1986). Ulwalamano olwenziwe ngolwakhiwo lwentsebenzo lubonakalise ukuba i-oxytocin-induced pireance erection yaxhaswa yi-uterinetype receptors ye-oxytocin, kunye ne-Ca2 + enempembelelo kwii-cell cells ze-oxytocinergic neurons ezixhomekeke kwimimandla yengqondo kunye ne-activation ye-nitric oxide-synthase. I-oxide ye-nitric ngokubamba njengesithunywa se-intracellular ngeendlela ezingaziwayo (ezingabandakanyi i-guanylate cyclase) zikhokelela ekusebenziseni i-neurons ye-oxytocinergic eyenza i-spinal cord kunye neendawo ezingaphezulu ze-brain-hyppothalamic, ekunciphiseni i-penile erection (Fig. 1) (bona ngezantsi kunye neArgiolas kunye noMelis, 1995, 2004, 2005 kunye neenkcukacha zayo). Ikhono le-oxytocin ukwenza i-neurons yayo isebenze

Umzobo 1. (UKUKHUMA) Ukumelwa kweSymmatic neurons, okuvela kwi-nucleus ephambili ye-hypothalamus kunye neprojekthi kwiindawo ezingakumbi zeengqondo ezinjenge-spinal cord, i-VTA, i-hippocampus, i-amygdala, njl. Ukusetyenziswa kwala ma-neurons i-dopamine, i-amino acids acitatory, i-oxytocin ngokwayo, i-hexarelin peptides e-analogue kunye nee-peptide ezithathwe yi-VGF zikhokelela ekukhutsheni i-penile, ezinokunciphisa kunye / okanye ukupheliswa yi-GABAergic, i-opioid kunye ne-CB1 receptors. Ukusebenza kwee-oxtocinergic neurons kusekondari kwi-activation ye-nitric oxide-synthase ekhoyo kulezi neurons. Eneneni oksayidi iqala nitric akhiwa ukukhuthazwa dopamine, excitatory acid acid okanye receptors yioxytocin okanye oxide zithe zadala-nitric oxide, njengokuba zivela kubaxhasi-nitric oxide enikwe ngqo ngumongo paraventricular, enza iiseli zemithambo-luvo oxytocinergic yi indlela kodwa abangaziwayo, kubonakala akazalani ukuvuselela i-guanylate cyclase. Oku kubangela ukukhululwa kwe-oxytocin kumgca wesipelini kunye nakwezinye iingingqi zengqondo. Ezinye iinkcukacha malunga nendlela i-oxytocin eyenza ngayo i-penile erection xa ikhutshwe kule mimandla, umzekelo, i-VTA, i-subiculum ye-ventral kunye ne-amygdala ichazwe kwicandelo leengcinga zeengqondo. Apha, i-oxytocin yenza izenzo zayo kunye nokwandisa akukho mveliso, ekhokelela ekuvelweni kwe-penile efumaneka kwi-PVN. Nangona kunjalo, ngokungafani ne-PVN, kwi-VTA ye-caudal ayikho i-guanylate cyclase esebenzayo. Oku kubangela ukwanda kwinkxalabo ye-cGMP ekhokelela ekusebenziseni i-nelions ye-mesolimbic ne-penile erection. Kwi-VS AYI isebenzela i-glutamatergic neurons eyenza indawo ezizezinye ze-hippocampal, kuquka i-VTA. I-Glutamic acid kwi-VTA isebenza ngokubonakalayo kwi-neuron eyelimbic ne-dopaminergic efumaneka kwi-oxytocin. Iinkqubo ezifana nezo zichazwe ngasentla ziyakuthi zisebenze kwakhona xa ukulungiswa kwe-penile kuvela kwiimeko zomzimba, okufana nokuba xa iigwane zendoda zifakwa phambi kobhinqa abangenako ukufumana (umz.

kwi-nucleus yecalastiki yayisekelwe kwizifundo ezibonisa ukuba: (1) i-oxytocin receptors zikhoyo kule nucleus ye-hypothalamic (Freund-Mercier et al., 1987; Freund Mercier kunye neSececkel, 1995); (2) i-oxytocin inceda ukukhululwa kwayo kwi-vitro nakwi-vivo (Freund Mercier noRichard, 1981, 1984; Moos et al., 1984); kwaye (3) i-oxytocin iyakhupha i-neurons yayo ngokusebenza kwi-nucleus ephambili (Yamashita et al., 1987). Ukongezelela, i-oxytocinergic synapses ezithintela kwiiselula ze-magnocellular oxytocinergic neurons ziye zafunyaniswa kwi-nucleus ye-parapotricular and supraoptic ye hypothalamus (Theodosis, 1985). Ekugqibeleni, ukutshabalalisa i-oxytocinergic neurons nge-electrolytic okanye i-chemical excitotoxic izilonda ze-nucleus ebonakalayo, ephazamisa ngokupheleleyo i-oxytocin kwinkqubo yesantya kunye nomgudu womgogodla, ayiphumelelanga kuphela umphumo we-oxytocin, kodwa uyonakalisa i-penile yokwakheka kunye nokungahambisani nokungathintani (jonga ngezantsi kunye no-Argiolas et al., 1987a, b; Liu et al., 1997 kunye neenkcukacha zayo). Iziphumo ezifana nezo zifumaneke zizilonda ze-nucleus ezibonakalayo zifunyenwe ziphikisana kunye ne-oxytocin receptor. Enyanisweni, ezi zixhobo ezifakwe kwi-nucleus yeparancial in nanogram zithintela ukulungiswa kwe-penile e-oxytocin ngokupheleleyo, nangona xa kunikwe i-ventricles e-latrical, akuthinteli kuphela ukunyuka kweepenile okubangelwa yi-oxytocin ngokwayo, kodwa kunye ne-e-penile erection (iCandelo 3 ngezantsi) kunye no-Argiolas no-Melis, i-1995, i-2004, i-2005 kunye nezikhombisi-ndlela) kunye nokungahambisani nokunganyaniseki (uMelis et al., 1999a), kwaye kwakhona kusebenza ngokugqithiseleyo ukuphazamisa ukuziphatha okukodwa kwimizimba yamadoda (Argiolas et al., 1988). Ukongezelela, ukusebenzisana ngokwesondo kuya kwandisa i-FOS, imveliso yemfuza ye-gene yangaphambili ye-gene c-fos kwi-neurons eyakhela i-oxytocinergic neurons eyenza umgca wokugcoba ochaphazelekayo ekulawuleni ukulungiswa kwe-penile (jonga iWitt ne-Insel, i-1994 kunye neenkcukacha zayo). Ekugqibeleni, ukungahambi ngesondo (umz., ukungakwazi komlingani omdala ukuba alandele i-estrogen-progesteroneprimed female receptive) hnjengoko kudibaniswe kwinkonzo yindoda enezinga eliphantsi le-oxytocin mRNA kunye ne-nitric-oxide synthase kwisiqalo se-paraventricular ye hypothalamus (Benelli et al., 1995; Arletti et al., 1997) (ukuphononongwa ngokubanzi kwezi zifundo ubone Argiolas, 1999; Argiolas kunye noMelis, 2004, 2005).

2.2. Ummandla we-ventral tegmental

Ummandla we-ventral tegmental ufumaniswe nje nje nje nje njengendawo yesifo sengqondo apho i-oxytocin inokukhupha i-penile erection. Lo mmandla uqulethe iziphetho zentsholongwane ye-oxytocinergic ezivela kwi-nucleus ne-oxytocin receptors (Freund-Mercier et al., 1987; Vaccari et al., 1998). Ngokuchanekileyo, i-oxytocin yafunyanwa ikwaziukukhupha i-penile erection xa ijojowe nge-unilaterally ibe yi-caudal, kodwa kungekhona kwindawo ye-rostral ventral ngendlela exhomekeke kumthamo (Melis et al., 2007). Amanqanaba asebenzayo aphezulu kunezo zinto ezifunekayo xa zijojiswe kwi-nucleus epalaseri kwaye zifana nezo zenza i-penile erection xa ijojowe kwi-subiculum ye-hippocampus okanye kwi-coreeromedial cortical nucleus ye-amygdala (jonga ngezantsi). Kuyabonakala ukuba umphumo we-prorebtile uhambelana ngokusebenza kwe-nelionic eyelimbic neoponergic neurons eyenza igobolondo ye-nucleus accumbens, leyo leyo isebenza ngokungaziwayo ngeendlela ze-neural ezibonisa ukuba i-incerto-hypothalamic ne-neoponergic neurons ezifaka i-neurons e-paradicion e-mediation i-penile erection (Melis et al., 2007, 2009a).

Ngokuphathelele indlela eyenziwa ngayo i-oxytocin eyenza i-dopaminergic neurotransmission kwindawo ye-ventral zone, idatha ekhoyo ibonisa ukuba i-oxytocin ivuselela i-oxytocinergic receptors esezisegulini zamaseli e-mesolimbic ne-dopaminergic neurons. Oku kwandisa i-Ca2 + impembelelo ngaphakathi kwamalungu eseli e-dopaminergic neurons, ngaloo ndlela isebenzisa i-nitric oxide-synthase (i-Succu et al., I-2008). Ngokungafani nucleus yecyrusus (jonga iCandelo 3 elingezantsi), i-nitric oxide ivulela i-guanylate cyclase, oko kukunyusa i-GMP ye-cyclic. Ngokuhambelana nale ndlela, mhlawumbi d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, umphikisi omkhulu we-oxytocin, okanye i-S-methyl-thio-l-citrulline, inhibitor enamandla ye-neuronal nitric oxide-synthase, injected into indawo ye-ventral tegmental phambi kwe-oxytocin, isusa i-penile erection kunye nokwanda kwe-cell-concentration ye-dopamine ingxube kwi-shell ye-nucleus accumbens eyenziwa yi-oxytocin. Ngaphezu koko, i-8-bromo-cyclic GMP, i-analogue esebenzayo ye-phosphodiesterase esebenzayo ye-phosphodiesterase, ikhuthaza ukunyuka kwe-penile xa ijojowe kwindawo ye-ventral ye-ventral kwaye ikhulise ingxube ye-dopamine yamasebe kwi-shell ye-nucleus accumbens, efunyenwe ne-oxytocin injected into indawo ye-ventral tegmental (Succu et al., 2008; Melis et al., 2009a) (jonga kwakhona umzobo 2).

Njalo ngokuhambelana nale ndlela, i-haloperidol, i-dopamine enamandla kakhulu ye-D2 receptor antagonist, injected kwi-shell ye-nucleus accumbens iyanciphisa i-penile erection eyenziwa yi-oxytocin injected endaweni yecala (Melis et al., 2007). Iindlela ezi ngasentla zixhaswa nezifundo eziphindwe kabini ze-immuno-fluorescence, ezibonisa ukuba i-oxytocin fibers ifuna i-cell cells ye-dopaminergic neurons kwindawo ye-ventral tegmental, eyayibhalwe ngaphambili nge-retrogracer tracer iFluorogold injected in shell of the nucleus accumbens ( Melis et al., 2007; Succu et al., 2008). Ukusebenza kwezi neuron ze-dopaminergic kunye ne-dopamine receptors kwi-nucleus accumbens zikhokelela ekusebenziseni iindlela ze-neural eziza kubonwa, ezikhuthaza i-incerto-hypothalamic ne-neoponeric neurons ukukhulula i-dopamine kwisiqulatho separagraphic, okwenza i-oxytocinergic neurons iqhube intambo yomgogodla kunye nokudibanisa ukulungiswa kwepenile (jonga ngasentla kunye no-Melis et al., 2007; Succu et al., 2007, 2008). Enyanisweni, i-oxytocin injected endaweni ye-caudal tegmental kwindawo eyenzayo eyenza ukukhutshwa kwe-penile, kwandisa ingxubevange ye-dopamine yecalaphinine kwi-dialysate ayifumanekanga kuphela kwi-nucleus accumbens, kodwa nakwi-nucleus ephambili (Succu et al., 2007).

2.3. I-hippocampus

Insimu ye-CA1 ye-hippocampus yayiyindawo enye yengqondo ecebileyo kwiimbumba ze-oxytocinergic kunye nama-receptors aboniswe kwizifundo zangaphambili apho ijozito ye-oxytocin yenze i-penile erection (bona iBuis, 1978; Sofroniew, 1983). Nangona kunjalo, ngokungafani ne-nucleus yombonakaliso, apha i-oxytocin yafunyanwa inokukwazi ukunciphisa ukulungiswa kwe-penile kuphela xa ijojowe ngokubanzi kunye nakwezinga eliphezulu kakhulu kunezo zifunyenwe kwi-nucleus yoluhlu (Melis et al., 1986; Chen et al., 1992). Izigulane ze-oxytocin kwi-subiculum zafunyanwa zingasebenzi kulezi zifundo zangaphambili. Nangona kunjalo, izifundo eziza kutshanje kwaye ziqaphele ngokukhawuleza zikhokelela ekuboniseni i-a ummandla we-subiculum apho umjovo we-oxytocin wawukwazi ukunciphisa i-penile erection ngendlela exhomekeke kumthamo (Melis et al., 2009b). Umphumo wepro-erectile we-oxytocin injected kule ngingqi yengqondo yaphawulwa ngamayeza afana nalawo afunyenweyo kwindawo ephethe indawo emva kokufakelwa kwe-unilateral injection (Melis et al., 2007), njengoko kufunyenwe kwinucleus. Ngokusobala, i-oxytocin injected into subiculum ventral ikhuthaza ukulungiswa kwe-penile ngokusebenzisa i-oxytocinergic receptors kwi-neurons equkethe i-nitric oxide-synthase, eyenza ukwanda kwe-nitric oxide production. I-oxide ye-nitric ngokubanjiswa njengesithunywa se-intercellular isebenzise i-glutamic acid neurotransmission, ekhokelela ekuhlanjeni i-penile, mhlawumbi ngokusebenzisa i-neural (glutamatergic) ebonakalayo kwi-subiculum ye-ventral kwimimandla yengqondo ye-hippocampal yokucwangcisa umsebenzi we-mesolimbic neoponergic neurons (umz., indawo ye-ventral zone, i-corrox ye-prefrontal, i-nucleus ephambili) (jonga ngezantsi kunye ne-Melis, 2007, 2009b; Succu et al., 2008).

Le ndlela yesenzo ixhaswa yi-intra-cerebral microdialysis, ebonisa ukuba i-oxytocin injected into subiculum ye-ventures kwi-doses eyenza i-penile erection, kwandisa imveliso ye-nitric oxide kunye ne-extracellular i-glutamic acid concentration kwi-dialysate esuka kwi-subiculum ye-ventral (Melis et al. , I-2010) kunye ne-extracellular dopamine kwi-nucleus accumbens (i-Melis et al., I-2007). Ezi mpendulo zazingqiniswanga nje kuphela yi-oxytocin receptor antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, kodwa kunye ne-neuronal oxide-synthase inhibitor S-methyl-thio-lcitrulline kunye ne-nitric oxide eravoglobin kwi-subiculum imizuzu embalwa ngaphambi kwe-oxytocin (uMelis et al., 2010).

Ngaphezu koko, ngokuhambelana nale ndlela yokusebenza, ukusetyenziswa kwe-glutamatergic neurotransmission yi-NMDA ejoyiweyo kwi-subiculum ye-ventral yenza i-penile erection (Melis et al., 2010). I-phenotype yezinto ezibonakalayo ezivela kwi-subiculum ye-ventral, ebangela ukuba kusebenze i-nelionic eyelimbic ne-neurons kunye nokwanda kwe-cellular dopamine kwi-nucleus accumbens, engaziwayo okwangoku. Nangona kunjalo, ekubeni i-penile erection eyenziwe yi-oxytocin injected into subiculum ye-ventor iyenzeka ngokukhawuleza kwenyuka ye-acutamic acid esele i-dialysate kwimihlaba ye-ventral, kodwa ingekho kwi-nucleus accumbens kwaye ixhatshazwa yi (+) MK-801, umxhasi ongeyomncintiswano onamandla wokunciphisa i-amino acid receptors ye-NMDA subtype (i-Woodruff et al., i-1987), injected endaweni ye-ventral zone, kodwa kungekhona kwi-nucleus accumbens (jonga i-2 ne-Melis et al., 2009b) , U mhlawumbi ukuba ezi zikhokelo zikhokelela ekusebenziseni i-glutamatergic neurotransmic endaweni ye-ventral tegmental, ephinde ibenze i-mesolimbic ne-dopaminergic neurons eyenza i-nucleus accumbens. Ingaba ukwanda kwe-acid ye-glutamic efunyenwe kwingingqi ye-ventral emva kwe-oxytocin injection kwi-subralulum ye-ventral ikhishwa kwi-neurons evela kwi-subiculum okanye kwezinye iindawo zeengqondo (umz., I-corrox ye-prefrontal) engaziwayo okwangoku. Noko ke, Oku kubangela ukuba kusebenze i-nelions i-mesolimbic ne-dopaminergic neurons kunye nokukhululwa kwe-dopamine kwi-nucleus accumbens. Lapha ukusetyenziswa kwe-dopamine receptors kukhokelela ekusebenziseni i-incerto-hypothalamic ne-neurons ye-dopaminergic, ukukhulula i-dopamine kwi-nucleus yeparagraphics, ngaloo ndlela isebenze i-oxytocinergic neurons eyenza umgca we-spinal kunye nokudibanisa i-penile erection (bona ngasentla kunye noMelis et al., 2007, 2009a; Succu et al., 2008).

2.4. Amygdala

I-amygdala yenye enye indawo yobuchopho inotyebi kwi-oxytocin fibers kunye ne-receptors (jonga i-Freund-Mercier et al., 1987; i-Vaccari et al., I-1998; i-Uhl-Bronner et al., I-2005). I-Oxytocin apha kucingelwa ukuba ibandakanyeke kwimisebenzi eyahlukeneyo, kwi-anxiolysis, kwimemori yoluntu kunye nokuqonda, ukufunda ngokuqiniswa koluntu, ukuvalelwa kwemvakalelo, ukuxubusha ubuso kunye nokwesaba kubantu ekusebenzeni kwe-erectile kunye nokuziphatha ngokwesondo (bona iKondo et al., 1998; iDominguez et i-2001; i-Ebner et al., i-2005; i-Huber et al., i-2005; i-Domes et al., i-2007; i-Petrovic et al., i-2008; i-Lee et al., i-2009; i-Donaldson ne-Young, i- 2009; i-Hurlemann et al. , 2010). Nangona kunjalo, ikhono le-oxytocin lenza ukuba i-penile yokwakhiwa kwinduku zendoda xa iqhutywe kwi-nucleus ye-posteromedial cortical ye-amygdala yafunyanwa nje kutshanje (Melis et al., 2009b). Le mpendulo yenzeke ngokukhawuleza ngokunyuka kwenkxuleko ye-dopamine eyongezelelweyo kwi-dialysate efunyenwe kwigobolondo ye-nucleus accumbens, efunyenwe emva kwe-oxytocin injection kwi-subiculum ye-ventric (Melis et al., 2009b). Inkqubo eyenziwa yi-oxytocin injected in the posteromedial cortical nucleus ye-amygdala ikhuthaza ukulungiswa kwe-penile engaziwayo okwangoku. I-data ekhoyo ebonisa ukuba ukwakhiwa kwe-penile kunye nokwanda kwintlukwano ye-dopamine eyongezelelweyo kwi-dialysate efunyenwe kwi-nucleus accumbens idibanisa ngokusetyenziswa kwe-oxytocinergic receptors, njengoko zombini izimpendulo zatshitshiswa yi-oxytocin receptor antagonist d (CH2) 5Tyr ( Me) 2-Orn8-vasotocin injected in amygdala nucleus ezimbalwa ngaphambi kokuba i-oxytocin (Melis et al., 2009b).

Naliphi na indlela i-oxytocin esebenzayo kwi-posteromedial cortical nucleus ye-amygdala, impendulo yesondo eyenziwe yi-peptide ipheliswa yi-blockade yazo zonke i-dopaminergic receptors ene-cis-flupenthixol injected in shell of the nucleus accumbens kunye nokuvalwa kwe-NMDA receptors kunye ( +) I-MK-801 injected endaweni ye-ventral zone, kodwa ingena kwi-nucleus accumbens, efunyenwe ukulungiswa kwe-penile eyenziwa yi-oxytocin injected into subiculum (ventis et al., 2009b). Oku kubonisa ukuba i-oxytocin injected kwi-posteromedial nucleus ye-amygdala isebenzise i-glutamic acid neurotransmission kwingingqi ye-ventral zone. Oku kubangela ukuba kusebenze i-nelions i-mesolimbic ne-dopaminergic, ekhokelela ekwakheni i-penile. Ngenxa yeengcamango ezibonisa iindlela ze-neural ezidibanisa le nucleus ye-amygdala kunye ne-subralulum ye-ventral (i-Canteras et al., I-1995; isiFrentshi kunye ne-Totterdell, i-2003), ezi ziphumo ziphakamisa ukuba kungenzeka ukusebenzisana phakathi kwezi ndawo zombini, nakuba Iindlela ezivela kwi-amygdala okanye kwi-nucleus accumbens okanye kwindawo yecala eliye lachazwa (uKelley kunye neDomesick, 1982; iWitter, i-2006).

2.5. Umgca womthambo

Umthambo womthambo ungenye indawo yinkqubo yesantya ephakathi ne-oxytocinergic fibers kunye ne-receptors (i-Freund-Mercier et al., I-1987; i-Uhl-Bronner et al., I-2005), apho i-oxytocin ikhuthaza ukulungiswa kwe-penile (Tang et al., 1998 ; Veronneau-Longueville et al., 1999; Giuliano kunye neRampin, 2000; Giuliano et al., 2001). Njengoko kukhankanywe ngasentla, ezi ntambo ze-oxytocinergic zivela kwi-nucleus yeparagraphicus ye-hypothalamus kwaye zenze igalelo ekuhlaleni iindlela zokulawula i-neurons yomgogodla yokuzimela. Ngokuqinisekileyo le miqulu yenza i-synaptic odibeneyo kwiphondo lokuguqula i-scandal sympathetic and parasympathetic columns kwinqanaba le-thoraco-lumbar kunye ne-lumbo-sacral kunye ne-neurons yomgogodla engenazo izilwanyana ezinobungqina be-penile cavernous (Marson noMcKenna, i1996; i-Giuliano kunye neRampin, i-2000; i-Giuliano et al. , 2001). Obuthelwano be-synaptic baboniswa ngokubhalwa kwee-spinal neurons ezivela kwi-penis baze bafinyelele intambo yomgudu ngamatrakta athile e-retrograde ajoyiweyo kwi-cavernous corpora, kunye ne-immuno-fluorescence kabili kunye ne-confocal laser microscopy (Tang et al., 1998; Veronneau-Longueville kunye al., 1999). Ngokuhambelanayo nalezi zifundo, kwiirats ezingamadoda ezingenasondlo ezingenayo i-intrathecal injection ye-oxytocin kwi-lumbo-sacral, kodwa kungekhona kwinqanaba le-thoraco-lumbar, lenze ukuba kubekho uxinzelelo olusenyongweni olusuka kwindlela exhomekeke kuyo. Le miphumo yabhujiswa ngokukhutshwa kwe-oxytocinergic receptor nge-d (CH2) 5Tyr (Me) 2-Orn8-vasotocin kunye necandelo leentsholongwane ze-pelvic (Giuliano noRampin, 2000; Giuliano et al., 2001). Ezi ziphumo zibonisa ukuba i-oxytocin, esebenza kwi-lumbo-sacral intambo yomgca, ikhulisa uxinzelelo lwe-intracavernous, kwaye icetyise ukuba i-oxytocin, ekhutshwe ngexesha lokusebenza komzimba kwiplasiyamu yombonakaliso ngumququzeleli onamandla we-spinal pro-erectile neurons ezixhomekeke kwi-cavernous corpora. Kuyathakazelisa ukuba ezi zi-pro-erectile ze-spinal neurons apho i-oxytocin zenza umonakalo wayo we-erectile, nazo zifumana oonxibelelwano lwe-synaptic kwi-serotoninergic neurons ezivela kwi-nucleus paragigantocellularis yesakhiwo esicacile se-medulla oblongata (i-Marson no-McKenna, i-1992; iTang et al ., 1998). Ukutshatyalaliswa kwezi-neuron ze-serotoninicic kwenza kubekho i-ejaculation kunye ne-penile reflexes kwindoda zamadoda (Marson noMcKenna, 1992; Yells et al., 1992). Ekubeni iidakamizwa ezikhuthaza i-5HT2C i-receptors iququzelela ukulungiswa kwe-penile xa kunikwe i-intrarebroventricularly, kodwa ingekho kwi-nucleus epalaseri, kunye neziyobisi ezivimba i-5HT2C i-receptors nciphisa i-dopamine i-agonistand e-oxytocin eyenziwe i-penile erection, ngelixa i-dopamine izithinteli zinciphisa i-5HT2C i-agonist-induced penile erection ( ubona iSancancampiano et al., i-1994 kunye nezikhombisi-ndlela), kuye kwacetyiswa ukuba i-oxytocin iququzelela isenzo se-pro-erectile i-5HT2C i-receptors kwizinga le-lumbo-sacral intambo yomgudu (Stancampiano et al., 1994). Ngaphandle koko, i-oxytocin inokuchaphazela umsebenzi we-spinal descending serotoninergic neurons ngokusebenza ngokuthe ngqo kwi-nucleus paragigantocellularis, apho la ma-neurons avela khona (khangela iSancancampiano et al., 1994).

3. Intsebenziswano phakathi kwe-oxytocin, i-dopamine kunye ne-glutamic acid kwi-system central ne-nervous erection

Njengoko kukhankanywe kwiCandelo 1, zonke i-neurons ze-oxytocinergic ezikhoyo kwinkqubo ye-nervous central zivela kwi-nucleus ephambili kunye nezakhiwo ezijikelezayo. Umsebenzi wee-neurons ungaphantsi kolawulo lweeurotransmitter ezahlukeneyo kunye / okanye i-neuropeptides. Phakathi kwezona zifunyenwe kakhulu kumgangatho wepalasariki, i-dopamine, i-glutamic acid, i-gamma-aminobutyric acid (i-GABA), i-nitric oxide, i-endocannabinoids, ii-peptide ze-opioid, i-hormone yokukhula-ukukhulula iipepptide, iiproptides ezihlobene ne-VGF kunye ne-oxytocin ngokwayo. I-Dopamine, i-glutamic acid, i-hormone yokukhula ekhupha iipepptide, iiproptide ezivela kwi-VGF kunye ne-oxytocin zivuselela, umzekelo, ezi zihlanganisi kunye ne-agonists zenza i-penile erection xa ifakwe kwi-nucleus ephambili, ngelixa i-GABA, i-pepides i-opioid kunye ne-endocannabinoids ingavinjelwa, umz. okanye iigonists zabo zivimbela ukulungiswa kweepenile (bona iMeisel noSachs, i1994; iWitt kunye neNtsana, i1994; iArigio kunye ne-Melis, i1995, i2004, i2005; i-Giuliano kunye neRampin, i2000, i2004; i-McNenna, i2000; i-Anderson, i-2001; i-Hull et al., i-2002).

Imida emininzi yobungqina bokuhlola ibonisa ukuba i-neurons ye-oxytocinergic kunye ne-neurotransmitters ne-neuropeptides ezingentla zibandakanyeka ekulawuleni umsebenzi we-erectile kunye nokuziphatha ngokwesondo kwiimeko ezahlukahlukeneyo zomzimba. Ngaphezu koko, i-oxytocin ekhutshwe kwiindawo ezinengqondo ezingaphezulu kwe-hypothalamic, ezifana ne-ventral tegmental, indawo ye-hippocampus kunye nemimandla yayo, i-amygdala kunye nentambo yomgogodla inokuchaphazela umsebenzi waleo neurons apho i-synopses i-oxytocinergic iminge. Okwangoku, i-neurons kuphela ebalulekileyo ukulungiswa kwe-penile apho i-oxytocinergic synapses impinge, echongwe ngokuqinisekileyo, yimizimba yeseli ye-mesolimbic neurons ye-daraminergic neurons ye-caudal tegmental endaweni ejongene nengqungquthela ye-nucleus accumbens (i-Melis et al., I-2007 ; Succu et al., 2008), kunye ne-nerectile spinal neurons ezivela kwi-lumbo-sacral kwi-cavernous corpora (jonga i-Giuliano kunye neRampin, i-2000; i-Giuliano et al., I-2001) (jonga kwakhona iiCandelo 2.2 kunye ne-2.5) . Enyanisweni, nangona i-syntose i-oxytocineric kunye ne-receptors ziye zachongwa kwi-subiculum ye-ventral, i-amygdala kunye nentambo yomgogodla, iindawo ezibaluleke kakhulu ukulungiswa kwe-penile (jonga ngasentla), kule mimandla uhlobo lwe-neurotransmitter / present in the neurons apho i-oxytocinergic neerve endings impinge, ingaziwa.

Eli candelo lenkqubo yokuphonononga lushwankathela ngokufutshane iincwadi zakutshanje malunga neendlela ezisisiseko se-erectile ye-oxytocin ejoyiweyo kwindawo yendawo yokuqhayisa i-caural, i-subiculum ye-ventral ye-hippocampus kunye nentambo yomgogodla. Ukuqwalaselwa ngokukodwa kwintsebenziswano yep peptide kunye ne-dopamine kunye ne-glutamic acid kule mimandla kunye nendima ekusebenzisaneni ngayo kunokudlala kwindawo ephakathi komsebenzi we-erectile. Isishwankathelo esifutshane semiphumo ye-dopamine kunye ne-glutamic acid kwi-neurons ye-oxytocinergic kwi-nucleus ephambili, ekwadlala indima ephambili kumsebenzi we-erectile unikezelwa kuqala, ukwenzela ukuba umfundi abe nolwazi ngolu hlobo lophando lwangaphambili kule ndawo, njengoko ezi zifundo sele zihlolwe ngokubanzi (jonga uArgiolas noMelis, 1995, 2004, 2005; uMelis noArgiolas, 2003). Kwakhona kule nkalo, ingqwalasela enikwe ingqalelo kwimiphumo yamuva, ebonisa ukuba indima ebalulekileyo inxibelelwano ye-dopamine-oxytocin kunye ne-glutamic acid-oxytocin unxibelelwano kungekhona kuphela kwisenzo socansi (ukulungiswa kwe-penile kunye nokuqulunqa), kodwa nakwezesondo ukuvuselela nesondo.

3.1. Ukusebenzisana kwe-Dopamine-oxytocin kwisucleus yecala

The ubuchule be-dopamine agonists ukunyusa i-penile erection ngokusebenzisa i-neuron e-oxytocinergic ephakathi yaphakanyiswa emva kokufumanisa ukuba i-apomorphine inokukhupha i-penile erection xa ijoyikwe kwinucleus yecalaseli (Melis et al., 1987) xa i-oxytocin receptor antagonist d (CH2) i-5X (Me) i-2-Orn8-vasotocin injected intrarebroventricularly (icv) iyakwazi ukunciphisa phantse i-penile erection engenziwanga kuphela yi-oktotocin eyanikezwa i-icv, kodwa nayo i-apomorphine, enikwe ngaphantsi (Argiolas et al., 1987b). Ezi ziphumo zalandelwa zizo ezinye iziphumo ezibonisa iziphumo ezifanayo xa d (CH2) 5Tyr (Me) 2-Orn8-vasotocin yanikezwa i-icv ne-apomorphine yanikelwa ngqo kwi-nucleus yeparagraphic (Melis et al., 1989b), lukuqala ukubonisa ukuba i-dopamine i-agonists ikhuthaza ukulungiswa kwe-penile ngokusebenzisa i-neurons ye-oktocinergic neurons eyenza i-portographicic neurons ezixhomekeke kwimimandla yengqondo yengqondo kwaye ngokukodwa kwintambo yomthambo (bona uArgiolas noMelis, 1995, 2004, 2005). Ngokuhambelana nale ngcamango, kwiingqungquthela ezingasondelanga, ukukhutshwa kwe-lumbo-sacral i-oxytocinergic receptors yi-non-peptide receptor antagonist sele ifunyenwe ukukwazi ukuphelisa i-apomorphine-induced rises in intracavernous ingcinezelo eyenziwa yi-dopamine agonist apomorphine, ukubonelela ubungqina i-paraventriculo-spinal oxtocinergic pathway ebandakanyeka kwipenile erection (Baskerville et al., 2009).

Izifundo ezijoliswe kuyo ukuchongwa kwe-dopamine receptor ejongene nokuqulunqwa kwe-penile erection, kuboniswe ukuba kwimeko ye-nucleus dopamine receptor i-agonists eyenza i-penile erection ngokwenza i-dopamine receptors yentsapho ye-D2, njengoko kufumaneka nge-dopamine receptor agonist enikezelwe inkqubo (bona uMelis et al., 1987; Eaton et al., 1991; uMelis noArgiolas, 1995a). Ngako-ke, i-apomorphine, i-aponorroine, i-D1 ne-D2 i-agonist receptor, kunye ne-quinpirole, i-quinpirole ekhethekileyo, i-agonist, kodwa i-SKF 2, i-D38393 receptor receptor receptor receptor, i-nucleus ifunyenwe ukukwazi ukunyusa i-penile erection , kwaye impendulo yesondo eyenziwe yi-D1 receptor agonists yachithwa yi-D2 i-receptor antagonists, njenge-haloperidol kunye ne-l-sulpiride, kodwa kungekhona ngu-SCH 2, umxhasi we-D23390 we-receptor antagonist (uMelis et al., 1). Ikhono lokwenza i-apomorphine ukwenza i-penile erection xa ifakwe kwi-nucleus yombonakaliso yabuye yaqinisekiswa ngophando lwe-telemetry olubonisa ukuba i-dopamine agonist enikwe i-nucleus ebonakalayo iyakwazi ukwandisa uxinzelelo lwe-intracavernous ekuvukeni kwamagundane ngaphandle kokuguqula uxinzelelo lwegazi (Chen et al. , I-1987; i-Giuliano kunye no-Allard, i-1999), njengoko ifunyenwe emva kwe-injection system (Bernabè et al., 2001). Ezi zifundo nazo baqinisekisile indima ebalulekileyo ye-D2 receptors, njengoko i-D1 i-receptor receptor yayifumaneka ukuba ayikwazi ukunyusa uxinzelelo lwe-intracavernous xa ijojowe kwinucleus (Chen et al., 1999).

Kukho ubungqina obuninzi bobuchule bokuhlola obufumanekayo ukubonisa ukuba i-paraxistular D2 receptors, ekhuthaza ukuba i-penile erection, ibekwe kumaziko eseli e-oxytocinergic neurons. Okokuqala, i-nucleus yeparagraphic iqukethe i-dopaminergic nerve terminals ebizwa ngokuba yi-incertohypothalamic ne-dopaminergic neurons. Amalungu eseli la ma-neurons asele A13 ne-A14 iqela I-Dahlstrom ne-Fuxe (1964), iqhubise ngokubanzi kwaye ingabonakaliyo izakhiwo ze-hypothalamic ezininzi, ezibandakanya i-neuron ene-oxytocinergic neuron engxenyeni ye-neurohypophysis kunye / okanye kwiindawo ezingqondweni ze-hypothalamic (Buijs et al., 1984; Lindvall et al., 1984).

Ukubandakanyeka kwezi-neuron ze-dopaminergic kwinqanaba lepalasariki ekulawuleni ukulungiswa kwe-penile kunye nokuxhaswa kuxhaswa yi-microdialysis zophando ezibonisa ukuba i-dopamine ye-extracellular kunye ne-3,4-dihydroxyphenylacetic acid (i-DOPAC), i-metabolite yayo eyona mveliso yanda kwi-dialysate efunyenwe i-nucleus yecalasti yeentlanzi zamadoda ezinobundlobongela obubonisa ukungahambisani nokungathintekiyo xa zifakwa phambi kwe-esrogen + ye-proroterone-eyamkelwa ngumfazi owamkelekileyo (uMelis et al., 2003).

Ukunyuka kwe-dopamine kunye ne-DOPAC iphakame ngakumbi xa ukuxubusha kunye nentombazana eyamkelekileyo yavunyelwa (uMelis et al., 2003), njengoko kufumaneke kwindawo yangaphambili (Hull et al., 1995) kunye nucleus accumbens (Pfaus kunye no-Everitt, i-1995). Okwesibini, uphando oluthile lubonisa ukuba ukulungiswa kwepenile okubangelwa ukukhuthazwa kweeplasi ze-D2, ezixhaswa yi-oxytocin ezikhutshwe kule mimandla. Ngako oko, i-apomorphine enikezwe ngamayeza okubangela ukuba i-penile erection, ifumaneke yakwazi ukwandisa i-oxytocin ingxube, kungekhona kwiplasma yamagundane kunye neenkwenkwezi (Melis et al., 1989a; Cameron et al., 1992), kodwa nakwimbongo indawo, njenge-hippocampus (Melis et al., 1990). Ngokuhambelana nale miphumo, i-apomorphine injected in nucleus paraventricular kwi-dose eyenza ukukhutshwa kwe-penile kutshanje kuboniswe ukuba iyakwazi ukwandisa i-nucleus accumbens, i-nucleus accumbens eyongezelelekileyo yeselula, igalelo elincitshiswe yi-oxytocin receptor antagonist d (CH2) I-5Tyr (Me) 2-Orn8-vasotocin injected endaweni yecala (Succu et al., 2007; Melis et al., 2009a) (jonga kwakhona iCandelo 4). Okwesithathu, izilonda zombini ze-electrolytic ze-nucleus ezibonakalayo, eziphantse ziphelise ngokupheleleyo i-oxytocin kwiindawo ezingakumbi zeengqondo (i-Hawthorn et al., I-1985), isusa i-apomorphine-induced penile erection (Argiolas et al., 1987a), kunye ne-oktocin receptor contraagonists kunikezelwa kwii-ventricle zangasemva, kodwa kungekhona kwi-nucleus yepalaseri, ukunciphisa i-dose-dependence e-apomorphineinduced erection e-potency efana neyo yale mihlanganisi ekhusela i-oxytocin receptors (Melis et al., 1989b). I-Oxytocin i-receptor antagonists nayo inamandla kakhulu ekunciphiseni ukuququzelelwa kwendlela yokuziphatha ngokwesini kungekho kuphela yi-oxytocin, kodwa nayo i-apomorphine (Argiolas et al., 1988, 1989).

Ngokuphathelele indlela i-D2 receptors eyenziwa ngayo i-dopamine okanye i-dopamine receptor agonists, ukwandisa umsebenzi we-oxytocinergic neurons, ngaloo ndlela ikhulule i-oxytocin kwimimandla yengqondo yengqondo kunye nasentanjeni yomgudu, ininzi yolwaziukuxhasa i-hypothesis yokuba ukuvuselelwa kwama-receptors e-D2 kwandisa ukuxinwa kwe-CaxNUMX + ions intracellular ngaphakathi kwamalungu eseli e-oxytocinergic neurons, ekhokelela ekusebenziseni i-nitric oxide-synthase, i-CaxNUMX + -calmodulin-enzyme exhomekeke kwi-enzyme, ekhoyo kule mizimba yeseli (iVincent neKimura, i-2; i-Torres et al., i-1992; i-Sanchez et al., i-1993; i-Sato-Suzuki et al., i-1994). Ukwandiswa kwemveliso ye-nitric oxide kubangela ukuba kusebenze i-oxytocinergic neurons. Ngako oko, (1998) i-apomorphineindine erection erection yathintelwa yi-block blockers ye-calcium kunye ne -_-conotoxin GVIA, i-blocker enamandla kwaye ekhethiweyo yeendlela ze-Ca1 + ze-N-type (uMcCleskey et al., 2) ezinikezelwa ngumbonakalo. i-nucleus (bona iArgiolas et al., i-1987, kunye neenkcukacha zayo); (I-1990) i-apomorphine eyenziwe i-penile erection yathintelwa yi-nitric oxide-synthase inhibitors enikezwe kwi-nucleus ephambili (Melis et al., 2c); kunye ne-1994) i-apomorphine kunye nezinye i-D3 i-aconist receptor ezinikezelwa kwii-dose ezenza ukuba i-penile erection yenze ukwanda kwemveliso ye-nitric oxide kwi-dialysate ye-paraalysis efunyenwe yi-microdialysis ye-intra-cerebral, ukwanda okwenziwe ngama-inhibitors we-nitric oxide I-D2 i-receptor i-agonistinduc erection penile (Melis et al., 2). Indlela yokusebenzisa i-nitric oxide eyenzela i-neurons ye-oxytocinergic neurons, ayisaziwa, nangona idatha efumanekayo ibonisa ukuba i-nitric oxide isithunywa se-intracellular kwaye i-guanylate cyclase ayibandakanyeki. Ewe, i-analogue esebenzayo ye-phosphodiesteraseresistant analogue ye-cyclic GMP, i-1996-bromo-cyclic GMP, yafunyanwa ayinakukwazi ukunyusa i-penile erection xa kunikwe i-nucleus ephambili (Fig. 8) (bona uMelis no-Argiolas, i-2b kunye neenkcukacha zayo).

Ingcaciso ekhankanywe ngasentla idlalwa njengento engaqinisekisiyo, ngokuyininzi kuba ukuvuselelwa kwe-dopamine i-D2 receptors idla ngokudibanisa nokuba yinto yokuxolisa yamalungu eseli e-neurons aqukethe la ma-receptors ngokusebenzisa iindlela ezahlukeneyo zeeprotheyini ze-G (khangela uSokoloff noSchwartz, 1995). Nangona kunjalo, inkcazo enokwenzeka malunga nale ngxabano, ehambelana nokukhuthazwa ngokuthe ngqo kwee-neononi zengxowankulu ye-oxytocinergic nge-dopamine, kuye kwacetyiswa ukuba kungekudala ukufumanisa G protein-ehlanganisiweyo yedopamine D4 i-receptor, ilungu lentsapho ye-D2 ye-receptor (D2, D3 kunye ne-D4), ukukhuthazwa okwandisa i-Ca2 + inxu lumene kwiilungiselelo zamaseli ezine-cloned version ye-subtype ye-receptor (Moreland et al., 2004). Okubaluleke ngakumbi, i-D4 receptor receptor agonist (umzekelo, i-ABT 724) (i-N-methyl-4- (2-cyanophenyl) i-piperazynil-3methylbenzamide i-maleate) ifumaneke inokukwazi ukunciphisa i-penile yokwakhiwa kwimikoko yamadoda xa inikezelwa inkqubo (uBrioni et al. 2004). Esi siphumo asizange sitholwe nge-D2 receptor subtype agonist PNU-95666E (R-5,6-dihydro-N, N-dimethyl-4Himidazo [4,5,1-i] quinolin-5-amine) (i-Hsieh et al., 2004), Kwakungenako ukunyusa i-Ca2 + impembelelo kumalungiselelo eseluneengqungquthela ze-D4 receptor subtype (i-Brioni et al., i-2004; i-Moreland et al., i-2004). Ngokuhambelana neengcamango ezingentla kunye neziphumo, i-PD 168,077 (i-N-methyl-4- (2-cyanophenyl) i-piperazynil-3methylbenzamide i-maleate), i-PIP-3EA (2- [4- (2-methoxyphenyl) ipiperazin-1-ylmethyl] imidazo [1,2-a] pyridine) kunye nezinye i-D4 receptor receptors (i-Heier et al., I-1997; i-Melis et al., I-2006b; iLöber et al., I-2009), yafunyanwa yakwazi ukunyusa i-penile erection xa ijojowe inkqubo, icv i-nucleus yeparagraphic, nangona ingaphumelelanga ngaphaya kwe-apomorphine. Impembelelo yepro-erectile yale-agonists ye-D4 yamkelekile yathintelwa ngu-L-745,870 (3- [chlorophenyl] piperazin-4-yl) -methyl-1H-pyrrolo [1-B] pyridine trihydrochloride), i-receptor ye-D2,3 ekhethiweyo umchasi (Patel et al., 4; Melis et al., 1997, 2005b; uLöber et al., 2006).

Ekugqibeleni, umphumo we-pro-erectile we-D4 receptor aconists apha ngasentla wancitshiswa nge-nitric oxide-synthase inhibitors, enikwe kwi-nucleus yerhasi, kunye ne-d (CH2) 5Tyr (Me) i-2-Orn8-vasotocin, i-oxytocin i-receptor antagonist unikezelwe i-icv kodwa kungekho kwinqanaba leparavista. Ezi ziphumo zihambelana neengcamango zokuthi i-D4 receptor receptor iyakhupha i-oxytocinergic neurons ngokusebenzisa i-nitric oxide-synthase, kwaye ikhulula i-oxytocin kwimimandla yengqondo yengqondo, leyo leyo eyenza i-penile erection, njengokuba kuboniswe i-apomorphine kunye ne-classic D2 agonists (uMelis et al ., 2005, 2006b; uLöber et al., 2009).

Iziphumo ezingentla zixhasa nenkqubela yokuba i-dopamine ikhuthaza ukulungiswa kwe-penile ngokubamba kwi-receptors ye-D4 esekweni yamaseli e-neuron e-paradicion oxidicinergic, kwaye eyabangela ukwanda kwe-Ca2 + kwimizimba yamaseli ye-oxytocinergic neurons, ekhokelela ekuveleni kwe-nitric oxide production. I-oxide ye-nitric isebenzisa i-oxytocinergic neurons ukukhulula i-oxytocin kwimimandla yengqondo engaphezulu kunye ne-spinal cord, njengoko sele ixoxwe. Ngale ndlela, Kuyaphawuleka ukuba i-dopamine receptors sele ichongiwe kumalungu eseli e-oxytocinergic neurons kwi-nucleus epalasariya ziva nje ngokuphinda kabili izifundo ze-immuno-fluorescence kunye ne-D2, i-D3 kunye ne-D4 receptor antibodies kunye ne-oxytocin antibodies. Ezi zifundo zibonise ukubonakaliswa kwazo zonke ezintathu ze-D2ii-subtypes (D2, D3 kunye ne-D4), edibanisa ngokuzimeleyo kwiiseli zeeseli ze-oxytocinergic neurons kwi-nucleus yeparagraphic (kunye nakwi-nucleus ephezulu kunye nommandla wangaphambili) (Baskerville kunye noDouglas, 2008; iBaskerville et al., 2009).

Oku kunika inkxaso enamandla ye-neuroanatomical ukuba kungenzeka ukuba i-dopamine kunye ne-dopamine receptor i-agonists yohlobo lwe-D2 yenza i-penile erection ngokusebenzisa i-neuron e-oxytocinergic ngokukodwa eyenza ingingqi ye-extrahypothalamic ekhunjulwe ngasentla, umzekelo, intambo yomgogodla, indawo ye-ventral zone, i-hippocampus kunye ne-amygdala. Nangona kunjalo, ezi ziphumo aziboneleli naluphi na uncedo malunga nokuchongwa kwe-D2 receptor subtype / s, evuselela i-erectile response. Ngelishwa, akukho ncedo lunokufumaneka nangakumbi kwizifundo ezijoliswe ekuboneni i-oxytocinergic neurons eyenziwe yi-dopamine receptor receptor kwi-nucleus epalasethi. Enyanisweni, naphezu kwemisebenzi eyahlukeneyo kwiindidi ze-dopamine receptor subtypes, okanye i-dopamine receptor agonists (umzekelo, i-apomorphine), okanye i-agonists ye-D2 ye-receptor (i-quinpirole, eyenziwa kuzo zonke i-D2 receptor subtypes) okanye i-D4 receptor aconists ukusetyenziswa kwee-neurons ze-oxytocinergic, njengoko kulinganiswa ngokunyuka kweprotheni ye-FOS kwi-parvocellular oxytocinergic neurons ye-nucleus ephambili (Bitner et al., 2006). Nangona kunjalo, oku kufunyaniswe ngoku kutshatyalaliswa, njengoko iprotheni ye-FOS yanda kwi-neurons ye-oxytocinergic ifunyaniswa kuphela xa i-penile erection yenziwe yi-quinerolane, eyenza ngokukodwa kwi-D2 kunye ne-D3 receptor subtypes, kodwa kungeyi-PD 168077, i-D4 receptor agonist, nangona ubuchule bezo zombini izixhobo zokubangela impendulo yesondo (Baskerville et al., 2009).

Uvavanyo olongezelelweyo kunye nee-agonists ezikhethiweyo zenye i-D2 receptor subtypes (ngokukodwa i-D2 kunye ne-D3) ziyimfuneko ukuba zichonge indima ecacileyo nganye ye-dopamine receptor subtype ekulawuleni umsebenzi we-erectile kwinqanaba lesiphakamiso. Kule nkalo, njengoko sele ikhunjulwe ngaphambili, i-apomorphine, eyenza ngokuphangaleleyo kuzo zonke i-dopamine receptor subtypes (bona uBrioni et al., 2004, kunye nezikhombisi zayo), iphumelela ngakumbi kunokuba i-D4 receptors i-agonist ekunciphiseni i-penile erection xa ijojowe kwisiqendu nucleus. Oku kunokuba kuchazwe ngokubambisana okuphezulu kwe-apomorphine kwi-receptors ye-D4 xa kuthelekiswa neyo-test ye-D4 receptor agonists, okanye enye i-D4 receptor receptor i-agonists ingenza njenge-agonists ye-D4 ye-aconist, okanye i-activation concomitant ye-dopamine receptor subtypes nge-apomorphine. ukuvelisa ukusetyenziswa okuphezulu kwee-oxytocinergic neurons ukudibanisa i-penile erection, kunokuba kusebenze yi-D2 receptor receptor ye-D4 receptor subtype kuphela.

Ukusebenzisana phakathi kwe-dopamine i-D1 kunye ne-D2 receptors sele sele ichazwe ekulawuleni ukuziphatha ngokwesondo kwinqanaba lommandla ongaphambili (jonga iHull et al., 1989). Kwimeko apho ukungakwazi ukukhetha i-D2 receptor i-agonists ukwenza i-penile erection (i-Hsieh et al., I-2004) iya kuqinisekiswa (kodwa ubone uDeortort et et., 2009), umzekelo, nangemva kokufakelwa kwileyi-compounds kwi-nucleus , indima enkulu kwi-receptors ye-D3 yedwa okanye kunye ne-receptors ye-D4 ekusebenziseni i-oxytocinergic neurons yokudibanisa i-penile yokwakhiwa kufuneka ihlaziywe ngokubanzi (jonga iBaskerville et al., 2009). Ngelishwa, i-D2 kunye ne-D3 receptor agonists (umz., Eyahlukileyo kwimibandela yazo le mibini ye-receptor subtypes ubuncinane emine imiyalelo emihlanu ye-vitro) ayitholakali okwangoku. Ngesi sizathu, isiphakamiso samva nje sokuba i-D3 receptors idibanisa i-penile erection eyenziwa ngama-agonists ase-classic receptor agonists, esekelwe ngokukodwa kwi-D2 i-receptor antagonists echazwe kwii-vitro test, ukunciphisa ukulungiswa kwe-penile eyenziwa yi-D3 agonists, i-apomorphine, i-quinpirole kunye ne-pramipexole, eyenza ngokukhawuleza zonke i-dopamine i-D2 receptor subtypes (i-Collins et al., i-2), ngokuqinisekileyo imfuno kufuneka iqinisekiswe kunye nezinye izilingo. Le mfuneko iyadingeka nangenxa yokuba akukho mpembelelo ye-agonists ye-D4 kwi-penile erection efunyenwe kulolu cwaningo, ngokuchasene ngokugqithisileyo neziphumo zezifundo ezikhankanywe ngasentla, ezibonisa umphumo we-prorebtile we-D4 receptor agonists. Enyanisweni, kwanokuba amandla okwenza i-apomorphine iqhube i-penile erection (kunye ne-inwning) kwi-D4 i-knockout pice kunye ne-potency efana neyo yabonwa kwintlobo ye-D4 ye-knockout mouse kunye nekhono le-D3 yokumelana nabamkeli ukuphelisa impomorphine impendulo kwizilwanyana ( I-Collins et al., I-2009) ayinakuqwalaselwa njengobungqina obucacileyo kwendima ekhethiweyo ye-D3 receptor subtype kwi-D2 i-receptor-incuted erection pension. Ulwahlulo lweentlobo ngaphandle, izifundo kunye neurotransmitter / neuropeptide kunye / okanye i-neurotransmitter / neuropeptide i-receptor gene ablation (i-neurotransmitter / neuropeptide kunye / okanye i-neurotransmitter / neuropeptide i-knockout izilwanyana) sele idibanise ukudideka kunye neengxaki ekuqinisekiseni indima ye-sexative ye-neurotransmitters kunye / okanye i-neuropeptides kunye ne-receptors zabo. Ngokunjalo, i-oxytocin gene ablation ivelisa i-oxytocin ikhonkco ukuba iqabane kwaye ilandele ngokuqhelekileyo, njengokungathi i-oxytocin yayingadingekile ukulungiselela ukulingana nokuxubusha. Kwakhona i-homozygous female oxtocin knockout amagundane ibonisa ukulingana okuqhelekileyo kunye nokwahlukana, nangona kuphazamiseka okubonakalayo kokucheba ubisi (Nishimori et al., 1996; Young et al., 1996). Ukukhutshwa kwe-gene gene encoding neuronal nitric oxide synthase, kwakhona kuvelisa i-nitric oxide synthase ikhonkce iigundane ukuba iqabane lilandele ngokuqhelekileyo (Huang et al., 1993). Nangona kunjalo, ezi ziphumo zibonisa ukuba luphawu olubalulekileyo lwe-physiology yokuzalana, oko kukuthi, ukuhlengahlengiswa kweenkqubo ezibandakanyekayo ekulawuleni kwayo kwinqanaba eliphakathi nendawo.

Ukuxhamla okunjalo ngokuqinisekileyo kuvela kwimvelaphi yokuziphendukela kwemvelo, kuba iqinisekisa ukuhamba kweengqungquthela kwisizukulwana esilandelayo ukuze kusinde iindidi. Ngako oko, ukuba i-ablation ye-D4 i-gene receptor ayiguquli umphumo we-proreortile we-apomorphine, ibonisa ukuba i-D4 receptors, njenge-oxytocin kunye ne-nitric oxide, yimbalwa yabalamli abasebenza kwiinkqubo ezilawula umsebenzi we-erectile, kunokuba iphakamisa ukuba akukho nxaxheba kula ma-receptors ekulawuleni ukulungiswa kwe-penile kunye nokuziphatha ngokwesondo. Ukungaphumeleli kwe-D4 i-agonists ukudala ukulungiswa kwe-penile xa kunikezelwa inkqubo kwiinkwenkwe zendoda yeengxaki ezahlukileyo zichazwe nje ngenye i sifundo (Depoortère et al., 2009). Nangona kunjalo, ngokungafani nomsebenzi kaColins et al. (2009), kwaye ukwenza umfanekiso kwisabelo se-D2 i-receptor subtypes ekulawuleni ukulungiswa kwe-penile ephazamisayo ngakumbi, olu pho nonongo lubonisa ukuba ukukhethwa kwe-D3 i-receptor antagonist kunikezelwe ngokusemgangathweni kwakungenako ukunciphisa i-apenorph-induced pension erection Iingqungqingi zendoda zoxinzelelo olunzulu kwi-pro-erectile effect ye-apomorphine, ngelixa ukuphendula ngokwesondo (kunye nokwehla) kwaxhatshazwa ngumphikisi we-D2 u-L-741,626 (3 - [[4- (4-chlorophenyl) -4-hydroxypiperidin -1-yl] i-methyl-1H-indole), ekhokelela abalobi ukuba bacetyise ukuba i-D2 receptors, kunokuba bafumane i-D3 kunye ne-D4 receptors, abo badlala indima enkulu kwi-D2-induced penile erection (Depoortère et al., 2009). Ekugqibeleni, kungenzeka ukuba umonakalo we-dopamine receptor agonists kwi-oxytocinergic neurons edibanisa ukulungiswa kwe-penile, ubuncinane inxalenye, ayikho ngqo ngaphandle kokuqondisa, umzekelo, odibeneyo okanye ochaphazela utshintsho kwimisebenzi yamanye ama-neurotransmitter neuropeptides anakho ukulungelelanisa umsebenzi neurons ze-oxytocineric kwi-nucleus ephambili, ayikwazi ukupheliswa ngokupheleleyo.

3.2. Intsebenziswano yeGlutamic acid-oxytocin kwi-nucleus yeparagraphic

I-nucleus ephambili ye hypothalamus isisityebi kakhulu kwi-synapses equkethe i-amino acid e-excitatory njenge-neurotransmitter (umzekelo, i-glutamic acid kunye ne-aspartic acid) (Van Van Pol, 1991). I-amino acidative acids in this nucleus ifakwe kwimisebenzi emininzi, kubandakanywa ukulungiswa kwepenile kunye nokuziphatha ngokwesondo (Roeling et al., 1991; i-Melis et al., 1994b, 2000, 2004b). Ngaloo ndlela, i-N-methyl-d-aspartic acid (NMDA), i-agonist ekhethiweyo ye-NMDA receptor subtype, kodwa ingabi (±) -_- amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) , i-agonist ekhethiweyo ye-AMPA subtype receptor okanye (±) -trans (1) -amino-1,3-cyclopentane dicarboxilic acid (ACPD), i-agonist ekhethiweyo ye-metabotropic receptor subtype, yafunyanwa inokunciphisa i-penile erection xa ifakwe i-nucleus yeparagraphical of rats moving rats (Melis et al., 1994b). Umphumo we-pro-erectile we-948 MR Melis, A. Argiolas / Neuroscience kunye neziphumo ze-Biobehavioral 35 (2011) I-939-955 i-NMDA ivinjelwe ngu- (+) MK-801, umxhatshazi we-NMDA ongafuni ukukhuphisana (Woodruff et al., 1987 ), injected in nucleus paraventricular (Melis et al., 1994b). Ngokuhambelana nale miphumo, kwizifundo ze-telemetry ezijoliswe ekujongeni ukunyanzeliswa kwe-intracavernous, i-NMDA yafunyaniswa kakhulu kunokuba i-agonists yezinye i-excinatory amino acid receptor subtypes xa ijojowe kwi-nucleus ebonakalayo ekwandiseni ingcinezelo ye-intracavernosal ekuvukeni okanye kwiisundu zamadoda (Zahran et al., 2000; uKhen noTshints, i-2003).

Njengoko kuphakanyiswe apha ngentla ye-oxytocin kunye ne-dopamine, mhlawumbi ukuba i-NMDA receptors idibanisa ukulungiswa kwe-penile ikhona kwiiseli zeeseli ze-oxytocinergic neurons, ekubeni iziphelo ze-amino acid eziphelile ziphelela kwi-cell body cell cell in the nucleus (Van Den Pol, 1991). Ngokufanelana noko kwatholakala nge-dopamine receptor agonists, umphumo we-pro-erectile we-NMDA ngokucacileyo uhambelana nokusebenza kwe-oxytocinergic neurotransmission, echithwe ngumphikisi we-oxytocin d (CH2) 5Tyr (Me) 2-Orn8-vasotocin enikeziweyo icv, kodwa ayikho kwi-nucleus ephambili (sibone uArgiolas noMelis, 1995, 2004, 2005 kunye neziboniso kulo). Ngokufanayo, ukuqhutyelwa kwe-NMDA-induced activation of oxytocinergic neurotransmission yinto yesibini ekusebenziseni i-nitric oxide-synthase, kuba i-NMDA-eyenziwe i-penile erection ivimbela i-nitric oxide-synthase inhibitors (i-N-Nitro-N-methyll-arginine i-methyl ester ne-N- i-methyl-thio-l-citrulline) enikezwe kwinucleus, kunye ne-NMDA ifakwe kwi-nucleus epalaseliyo kwii-doses ezenza i-penile erection, kwandisa imveliso ye-nitric oxide kwi-hypothalamic nucleus (bona u-Argiolas no-Melis, i-1995, i-2004, i-2005 kunye neekhonkco ). Ngokuphathelele i-dopamine receptor agonists, i-NMDA yenza ukuba kusebenze i-nitric oxidesynthase ingaba yinto yesibini ukuya kwenyuka i-Ca2 + inxungulo kwi-oxytocinergic body cells ngokusebenzisa i-NMDA receptors e-Ca2 + enezithuthi, njengokuba kuboniswe kumalungiselelo amancinci amaninzi (ukuhlaziywa ubone iSnyder, 1992; I-Southam kunye ne-Garthwaite, i-1993; i-Schuman ne-Madison, i-1994 kunye neenkcukacha zayo). I-oksidi ye-nitric isebenza ngokutsha kwe-oxytocinergic neurotransmission (jonga ngasentla). Imvelaphi yezinto ezibonakalayo ze-glutamatergism ezenza i-neveronic euronicity erectional erectional ne-neuroanatomical kunye ne-electrophysiological bungqina, kodwa ubuncinci inxalenye ye-hippocampus (i-Saphier neFeldman, i-1987; i-Chen et al., I-1992) . Nangona umsebenzi oqhubekayo kubalulekile ukubonakalisa ngcono imvelaphi yezinto ezibonakalayo kwi-glutamatergic nucleus, ukubandakanyeka kwe-acutamic acid kwi-nucleus epalariyali ekulawuleni ukulungiswa kwe-penile kunye nokuziphatha ngokwesini kuxhaswa ngokucacileyo ngophando lwe-microdialysis. Ngako oko, i-concentrations eyongezelelweyo yamaseliti ye-glutamic acid kunye ne-aspartic acid yanyuswa kwi-dialysate efunyenwe kwi-nucleus yeparagraphic of rats yamadoda ebonisa ukungahambisani nokungavumelani xa kufakwa phambi kobuchule obungenakufikeleleka kwe-estrogen + i-progesterone-primed rats female rats (Melis et al., 2004b), i-penile erections eziphambene nokusetyenziswa kwe-oxytocinergic transmission (uMelis et al., 1999a, b). Ukwanda okunjalo kwafunyanwa kwaphakama xa ukuqubana nomfazi okwamkelekileyo kuvunyelwe (uMelis et al., 2004a). Ngokuhambelana nenkolelo yokuba umsebenzi owandisiweyo we-acino acid amino acratically occurs in nucleus paraventricular ngexesha lokulungiswa kwe-penile kunye nokuququzelela, ukuziphatha okungahambelani kunye nokuziphatha okuxilisayo (ngexesha apho kukho i-pulale erections eyenzekayo) kuncitshiswe ngokukhutshwa kwe-NMDA receptors kwi-nucleus epalaseri , kwaye le ncitshitshiswa ilandelwa ukuhla kwenyuka yemveliso ye-nitric oxide eyenzeka kule nucleus yoluntu kwiimeko eziphathekayo (uMelis et al., 2000). Ukwanda kwe-extracellular glutamic i-concentration yecondari yesibini ukuya kwehla kwe-GABA ukukhululwa kwi-GABAergic nerveic ending in the synopses exitatory acid synicses ezixutywe kwii cell cell cells, nazo zafunyanwa kwinqanaba leplastiki emva kokuvalwa kwe-CB1 i-CB1 i-CB141761, kunikezelwa kwii-ventricle zangasese okanye ngqo kwi-nucleus yamaplaseli kwii-doses ezenza ukuba i-penile erection (yabone i-Succu et al., i-2006; i-Castelli et al., i-2007). Ukwanda okunjalo kwaholela ekusebenziseni i-nitric oxide-synthase kwiiselumzimba ze-oxytocinergic neurons, kwandisa imveliso ye-nitric oxide. I-oksidi ye-nitric isebenzisa i-oxytocinergic neurons edibanisa ukulungiswa kwe-penile njengoko kuchaziwe ngasentla. Ngokuhambelanayo naloo ndlela, i-SR 141761A yenze i-penile yokwakhiwa yancitshiswa ngokukhutshwa kwe-NMDA receptors kunye ne-nitric oxide-synthase inhibitors, kodwa kungekhona ngokukhutshwa kwe-dopamine okanye i-oxytocin receptors kwi-nucleus yeparadri, ngeli xesha likhuselwe ukukhutshwa i-oxytocin i-receptors ephakathi ne-oxytocin receptor antagonists ezinikezwa i-icv

3.3. Ukusebenzisana kwe-Oxytocin-dopamine kwindawo yecala lokungena

I-Oxytocin inciphisa i-penile erection xa ifakwe kwi-caudal inxalenye yendawo ye-ventral kwindawo exhomekeke kuyo (Melis et al., 2007). I-dose esebenzayo kakhulu ejoyiweyo i-20 ng, ngelixa i-dose ephezulu ihlolwe yi-100 ng. Impembelelo ye-oxytocin ihambelana nokusetyenziswa kwe-oxytocinergic receptors, njengoko impendulo yesondo ichithelwa yi-injection yangaphambili ye-oxytocin antagonist d (CH2) 5Tyr (Me) 2-Orn8-vasotocin kwingingqi ye-ventral tegmental. Ezi zamukeli zihlala kwindawo yamaseli e-dopaminergic neurons, leyo iprojekthi ngokuyinhloko kwigobolondo ye-nucleus i-accumbens. Ngako oko, (1) izifundo eziphindwe kabini ze-immuno-fluorescence zibonisa ukuba kwiindawo ezinobungozi be-ventral tektal indawo ye-oxytocinergic fibers zixubene kakhulu kunye neeseli zee-dopaminergic neurons, uninzi lwazo zibhalwe kakuhle nge-tyrosine-hydroxylase kunye ne-retrograde tracer Fluorogold ngaphambili injected kwi-shell ye-nucleus accumbens (i-Melis et al., i-2007), kunye ne-2 indawo ye-oxytocin eyenza ukulungiswa kwe-penile iqhutyana ngokunyuka kwenyameko ye-dopamine eyongezelelweyo kwiseli ye-dialysate efunyenwe kwi-shell i-nucleus accumbens (Melis et al., 2007). I-oxytocin-induced pension erection iyenzeka ngokukhawuleza ngokunyuka kwimizi ye-nitric emveliso kwindawo engxenyeni ye-ventral, ibe zombini iimpendulo ezingaxhatshazwanga nje kuphela d (CH2) 5Tyr (Me) 2-Orn8-vasotocin kunye ne-nitric oxide synthase inhibitor S- i-methyl-thio-l-citrulline, kodwa kunye ne-_-conotoxin, i-blox-CaxNUMX + iziteshi ze-blocker, ezixhomekeke kwi-voltage, kunye ne-ODQ (2H- [1] oxadiazole [1,2,4-a] quinoxalin-4,3-enye), inhibitor enamandla ye-guanylate i-cyclase, yonke inikwe indawo ye-ventral tegmental ngaphambi kwe-oxytocin (i-Succu et al., i-1). Ininzi ye-Fluorogold imizimba yamaseli e-dopaminergic edibene ne-oxytocinergic fibers, efunyenwe ibe yinto enokuthi i-tyrosine hydroxylase kwindawo ye-ventral tegmental zone, yayibhalwe ngokufanelekileyo nge-nitric oxide-synthase ne-guanylate cyclase (i-Succu et al., 2008), i-oxytocin -upuced penile erection ingadibaniswa ngolu hlobo lulandelayo. Ukusetyenziswa kwee-oxytocinergic receptors kwizidumbu ze-dopaminergic nge-peptide kwandisa i-Ca2 + impembelelo ngaphakathi kwamalungu eseli we-dopaminergic neurons. Oku kusebenze i-nitric oxide-synthase, i-enzyme ye-CaxNUMX + -calmodulin exhomekeke kuyo, okwandisa imveliso ye-nitric oxide. I-oxide ye-nitric isebenzisa i-guanylate cyclase, ekhokelela ekugxininiseni kwe-GMP ye-cyclic. I-Cyclic GMP isebenzisa i-neurons ye-dopaminergic eyenza i-nucleus accumbens. Inxaxheba ye-cyclic GMP kwi-penile erection eyenziwe yi-oxytocin injected kwindawo ye-ventral tegmental ndawo ixhaswa yikhono le-8-bromo-cyclic GMP, i-analogue esebenzayo ye-cyclic GMP, eyenza i-penile erection xa ifakwe indawo yokuqhafaza ye-ventral, kunye nokwandisa i-dopamine engaphezulu kweselula kwi-dialysate esuka kwi-nucleus accumbens (i-Succu et al., i-2008; i-Melis et al., i-2009a). Oku kuhambelana neendlela apho i-nitric oxide isebenza ngayo i-oxytocinergic neurons kwi-nucleus yeparagraphicus, ekubeni i-8-bromo-cyclic GMP ayikwazi ukunyusa i-penile erection xa ijojowe kule nucleus (uMelis no-Argiolas, i-1995b). 2). Ngokumalunga neendlela ze-neural ezisebenziselwa yi-dopamine kwi-nucleus accumbens ekhokelela ekukhutsheni i-penile, ezi zisaziwa. Nangona kunjalo, idatha efumanekayo ibonisa ukuba le ndlela ivuselela i-dopamine neurotransmission kwi-nucleus epalasethi ye-hypothalamus. Ngako oko, ukulungiswa kwe-penile eyenziwa nge-oxytocin kwenzeka ngokukhawuleza kwenyuka kwi-dopamine engaphezulu kweselula kungekhona kuphela i-nucleus accumbens, kodwa nakwi-nucleus ephambili, kwaye iyaxhatshazwa yi-dopamine receptor antiagonist haloperidol injected into nucleus paraventricular (Melis et al., 2007). AKuya kubambisana, ezi ziphumo zixhasa ingcamango yokuba i-oxytocinergic neurons evela kwinucleus yecalaysiyali kwaye iqhubekela phambili kwindawo ye-ventral ye-ventral, xa i-oxytocin ekhutshwe kuyo ikhutshwe kule ndawo, ngaloo ndlela isebenzise inkqubo yokubonakalisa i-NO-cyclic GMP, leyo ibuye isebenzise i-nelioni ye-dopaminergic neurons (Melis et al., 2007, 2009a; Succu et al., 2008). I-Dopamine ekhutshwe kwi-nucleus i-accumbens ivulela i-neural pathways ekhokelela ekusebenziseni i-incerto-hypothalamic ne-neurons ye-dopaminergic, eyenza i-paraventricular ne-oxytocinergic neurons ejikeleza umgca wesipelingi ejikeleza i-penile erection. Ngexesha elifanayo, i-dopamine ekhutshwe kwi-nucleus ye-paravista ingasenza i-oxytocinergic neurons iqhubekele kwiindawo ezinengqondo ezininzi ezifana ne-ventral tegmental, i-hippocampus, i-amygdala kunye neminye indawo yengqondo.

Njengoko kukhankanywe apha ngasentla, ngokuhambelana nale ngcamango, i-apomorphine injected in nucleus paraventricular kwi-dose eyenza i-penile yokwakhiwa iphinde ikhulise ingxube ye-dopamine yeselula kwinucleus accumbens, isiphumo sancitshiswe yi-oxytocin receptor antagonist (CH2) 5Tyr ( ) I-2-Orn8-vasotocin ijojowe kwindawo yendawo ye-ventral (Succu et al., 2007; Melis et al., 2009a). Ngokubambisana, iindlela ezingasentla zengxowanqa zingabangela ukuba i-neural circuits circuitry iquka i-dopamine, i-oxytocin nezinye i-neurotransmitters (umzekelo, i-glutamic acid, jonga ngezantsi) ingaphembeli nje ukusebenza kwezesondo kuphela, kodwa nesishukumiso sezesondo kunye nesondo (jonga iCandelo 4).

3.4. Ukusebenzisana kwe-Oxytocin-glutamic acid kwi-subiculum ye-ventral ye-hippocampus

I-Oxytocin inciphisa i-penile erection xa ijojowe kwi-ventral, kodwa ingekho kwi-subiculum ye-dorsal, ngendlela exhomekeke kumthamo (Melis et al., 2009b). Impendulo yesondo ihambelana nokuvuselela i-oxytocin receptors, ichithwe yi-injection yangaphambili ye-d (CH2) 5Tyr (Me) 2-Orn8-vasotocin inikwe indawo efanayo ye-oxytocin, efunyenwe kwezinye iindawo zengqondo (jonga ngasentla) . Ngokubhekisele kwendawo yokufumana i-receptors, idatha ekhoyo ibonisa ukuba zihlala kwindawo yeeseloni ze-neurons ezizityebi kwi-nitric oxide-synthase.

Ngoko ke, uphando lwe-microdialysis lubonisa ukuba ukwakhiwa kwe-penile eyenziwa yi-oxytocin kwenzeka ngokuhambelana nokunyuka kwe-nitric umveliso we-nitric kwi-subiculum ye-ventral, kwaye le nyuko ipheliswa kungekhona nje ngepilisi ye-nitric oxidesynthase inhibitor S-methyl-thio-l-citrulline kunye ne-nitric oxide scavenger hemoglobin, kodwa kunye no-d (CH2) 5Tyr (Me) 2-Orn8-vasotocin, bonke banikwe kwindawo efanayo ye-oxytocin kwizilingo ezithintela i-penile erection (Melis et al., 2010). Okubaluleke ngakumbi, ukunyuswa kwe-penile eyenziwa nge-oxytocin kwenzeka kwakhona ngokunyuka kwenyameko ye-glutamic acid engaphezulu kwendawo ye-subiculum ye-ventral, ephikisana nxamnye ne-non-competitive NMDA receptor antagonist (+) MK-801 enikwe subiculum ventral (Melis et al., 2010). Ngokubambisana, ezi ziphumo zibonisa ukuba i-nitric oxide esanda kuvela, ngokusebenza njengomthunywa we-intercellular, yenza i-glutamic acid i-neurotransmission ekhokelela ekwakheni i-penile, mhlawumbi ngokusebenzisa i-neural imperence projections ii-subiculum kwiindawo ezingakumbi zengqondo ze-hippocampal. Ngokuhambelana nale ngcamango, I-NMDA ifakwe kwi-subiculum ye-ventra yenza i-penile erection ngendlela exhomekeke kumthamo, kwaye le mphulo ixhatshazwa ngokupheleleyo ngendawo yokuqala (+) MK-801, kodwa ingabi ngu-S-methyl-thio-l-citrulline , hemoglobin okanye d (CH2) 5Tyr (Me) 2-Orn8-vasotocin (Melis et al., 2010). Ngokumalunga neendlela ze-neural eziqhelekileyo ezijolise kwiindawo ezincinci zengqondo ze-hippocampal ezenziwe ngama-acino amino acids (oko kukuthi, i-glutamic acid) kwi-subiculum ye-ventral, mhlawumbi ukuba lawa ma glutamatergic, njengokuba uninzi lwama-hippocampal. Okwangoku, kunokucetyiswa nje ukuba le misebenzi igqithise umsebenzi we-mesolimbic ne-neurons, ibuye ilandelelanise umsebenzi we-incerto-hypothalamic dopaminergic neurons kwi-nucleus ephambili, ekhokelela ekusebenziseni i-oxytocinergic neurons ukulungelelanisa ukulungiswa kweepenile njengoko sele kuxoxwa ngazo (jonga ngasentla).

Ngako oko i-penile erection eyenziwa yi-ventral subiculum oxytocin ivela ngokuhambelana nokunyuka kwe-dopamine engaphezulu kwamaselula kwi-shell ye-nucleus accumbens, kwaye oku kunyuka, njenge-penile erection, kupheliswe ngu-d (CH2) 5Tyr (Me) 2- I-Orn8-vasotocin inikwe i-subiculum ye-ventral ngaphambi kwe-oxytocin (uMelis et al., 2009b). Ngaphezu koko, ekubeni i-ventral subiculum e-oxytocin eyenza i-penile erection iyancitshiswa ngu- (+) MK-801 injected endaweni ye-ventral zone, kodwa ingena kwi-nucleus accumbens (i-Melis et al., I-2009b) kwaye iyenzeka ngokukhawuleza kwanda kweso-cell i-glutamic acid kwindawo engxowankulu, kodwa kungekhona kwi-nucleus accumbens, ukuba zombini izimpendulo ezipheliswe ngu-d (CH2) 5Tyr (Me) -Orn8-vasotocin, injected subiculum ye-ventral phambi kwe-oxytocin (jonga i-3) kusenokwenzeka ukuba ukusebenza kwe-nelionic eyelimbic neoponergic neurons yinto yesibini ukuya kwandiswa kwe-glutamatergic neurotransgic kwindawo yokuqhubela phambili. Oku kuphakamisa ukuba ukusebenzisana kwe-glutamic acid-dopamine elawula ukulungiswa kwe-penile ikhona kwindawo yecala. Izifundo ezongezelelweyo ziyimfuneko ukuze kuqinisekiswe ukuba i-pro-erectile ye-glutametergic yeendlela ezivela kwi-subiculum ukuya kwindawo ye-ventral ngqo okanye ingangqali, oko kukuthi, ngokusebenzisa i-cortex okanye iindawo ezithile zobuchopho (bona iMelis et al., 2009b kunye neenkcukacha zayo). Ekubeni i-nucleus yeparavista ifumana i-glutamatergic projection kwi-hippocampus (jonga ngasentla kunye noSaphier noFeldman, 1987), kwaye I-glutamic acid isebenzisa i-neurons ye-oxytocinergic neerons ezibandakanya abo baxhamlayo kwindawo (bona u-Argiolas kunye noMelis, i-2005 kunye neenkcukacha zayo), kunye i-oxytocin kwindawo ye-ventral ekhupha i-penile erection kwaye yandisa umsebenzi we-mesolimbic dopaminergic neuron(khangela ngasentla), kuyalinga ukucinga ukuba i-pi-neurons ye-oxytocinergic ye-aravali ingabandakanyeka, ubuncinane kwinqanaba, ekusebenziseni i-nelions i-mesolimbic ne-dopaminergic neurons nge-oxytocin injected into subiculum (jonga iCandelo 4).

4. Amazwi okuphetha

Izifundo ezihlaziyiweyo ngasentla ziqinisekisa kwaye zandisa iziphumo zakudala ezibonisa ukuba kwindoda zamadoda i-oxytocin idlala indima ephambili ekulawuleni okuphakathi kwe-penile yokwakhiwa kwinqanaba le-nucleus ephambili ye hypothalamus kunye nentambo yomgogodla. Ingakumbi, ininzi kakhuluuphando lweepesenti lubonisa ukuba i-oxytocin ithonya i-penile yokwakhiwa kwakhona ngokusebenza kwezinye iindawo zengqondo, oko kukuthi, indawo yendawo ye-ventral, i-subralulum ye-ventral, kunye ne-posteromedial cortical nucleus ye-amygdala.

Kwinqanaba lesiphakamiso, into ebalulekileyo yokufumana mhlawumbi ukufunyanwa kwegama lazo zonke i-dopamine receptors zentsapho ye-D2 (i-D2, i-D3 kunye ne-D4) kumalungu eseli e-oxytocinergic neurons kwi-nucleus ephambili (nakwi-nucleus ye-supraoptic kunye indawo yangaphambili) (iBaskerville noDouglas, i-2008; iBaskerville et al., 2009). Oku kunika i-neuroanatomical eqinile inkxaso kwi-hypothesis yokuba i-dopamine kunye ne-dopamine receptor i-agonists ingasebenzisa i-oxytocinergic neurons ngokuchanekileyo echaphazelekayo kwimisebenzi ye-erectile kwaye ingaphangeli nje kuphela kwintambo yomgudu, kodwa nakwiindawo ezingakumbi zeengqondo ze-hypothalamic. Kule nto, kubalulekile ukufumanisa ukuba ukwandiswa kwe-dopamine receptor-induced augmentation in intracavernous ingcinezelo ngokunciphisa i-oxytocinergic receptors kwi-lumbo-sacral intambo yomgcini (Baskerville et al., 2009). Enyanisweni, nangona ubungqina obunjalo bufunyenwe kwiisundu zamadoda, ukufumana kufakazela ukusetyenziswa kwe-paraventriculo-spinal oxytocinergic endleleni echaphazelekayo ekubandakanyekeni kwe-dopamine receptor-induced penile erection. HNgapha kunjalo, kusekufuneka kuqinisekiswe ukuba i-penile erection eyenzelwe ukuvuselelwa kwe-dopamine receptors ekhoyo kwi-cell i-oxytocinergic body bodies iyisibini kumsebenzi we-dopamine receptor subtype yentsapho ye-D2 (i-D2, i-D3 okanye i-D4) okanye ukuba la ma-subtypes awamkelekileyo asebenzisana ekumodeni impendulo erectile, mhlawumbi ngeendlela ezahlukeneyo ngokuxhomekeke kumongo apho kuvela khona i-penile erection (see Moreland et al., 2004; Enguehard-Gueiffier et al., 2006; Melis et al., 2006a, b; Löber et al., 2009; Collins et al., 2009; Depoortère et al., 2009; Baskerville et al., 2009).

Olunye ulo olutsha olubalulekileyo kukuba i-oxytocin yenza ukuba i-penile erection ifakwe kungekhona kwinqanaba leparagraphicus okanye kwi-CA1 kwintsimi ye-hippocampus, kodwa nakwindawo yendawo ye-hippocampus, i-subiculum ye-ventral, kunye ne-posteromedial cortical nucleus ye-amygdala. Ezi ndawo zengqondo azizange zivavanywe kwizifundo zangaphambili ezibonisa ukuba i-oxytocin yanda ngokukhawuleza i-epenile erection iziqwenga kwindoda zendoda, nangona zifumana njenge-lumbo-sacral intambo yomgudu we-oxytocinergic projections ukusuka kwisiqulatho se-paraventricular. I-Oxytocin yafunyanwa ngokuqinisekileyo inokwandisa i-epenile erection episodes, eyenziwa kuma-rats angamadoda amakhulu ekungabikho naluphi na umonakalo wezocansi, njengalezo ezivela kubukho obufikelelekayo okanye obungenakufikeleleka (i-estrogen-progesterone). ukuqhutyelwa kwe-genitalia, ifakwe kwi-nucleus ephambili kunye ne-CA1 kwintsimi ye-hippocampus, kodwa kungekhona kwi-subiculum ye-dorsal, i-septum yesikhokelo, i-nucleus yecaudate, indawo yangaphambili ye-preoptic, i-nucleus ye-ventromedial kunye nenucleus enkulu (Melis et al. , 1986). Kuzo zonke ezi zifundo zepenile erection zivame ukubalelwa xa i-penis yavela kwi-penile sheath yongumntu owayengazi kakuhle unyango olunikeziweyo ngokukhawuleza ngexesha lokuzama okanye kamva ngokuqwalasela ukuhlolwa okurekhodiweyo kwividiyo kunye neefowuni zekhamera zevidiyo. Isiqendu ngasinye se-penile siphelela i-0.5-1 min kwaye ngokuqhelekileyo sihamba kunye nokulungiswa kwe-penile kunye / okanye i-hip flexions. Akukho luvavanyo olwenziwa rhoqo kulezi ziphulo ukuze kuqinisekiswe umphumo wamava ezesondo, ubudala okanye ukuba la ma rats angabelana ngokwasezantsi okanye abaphenduli abaphezulu kwi-pro-erectile effect ye-oxytocin injected kwiindawo ezahlukeneyo zobuchopho. Oku kusebenza nakwinkoliso yezifundo malunga nefuthe le-erectile yezinye i-neuropeptides kunye neziyobisi ezandisa ukwanda kweepeni ze-epeniode, kuquka i-dopamine agonists, i-amino acids, i-ACTH-MSH, i-hexarelin ne-VGF peptides. Nangona kunjalo, i-pro-erectile impembelelo yalezi zixhobo ziye zaqinisekiswa ngokuphindaphindiweyo ngeendlela ze-telemetry, ezenza ukuba kwenzeke ukunyuswa kwe-penile ngokunyuka kweengcinezelo ze-intracavernous ezenzeka ngokukhawuleza okanye emva kokulawulwa kwezi zixhobo ngeendlela ezahlukeneyo, oko kukuthi, inkqubo, i-intrarebroventricularly ngqo kwi-brain nuclei ethile, emva kokufakelwa kwengcinezelo ye-microtransducer ngqo kwi-cavernous corpora (bona uBernabè et al., 1999). Kwindawo yendawo ye-ventral, i-subralulum ye-ventral kunye ne-posteromedial nucleus ye-amygdala nayo i-oxytocin inokunyusa i-penile erection ngokusebenza kwi-oxytocinergic receptors. Oku kukhokelela ekusebenziseni i-nelionic eyelimbic ne-dopaminergic neurons ezivela kwindawo yecala lokutsala kunye nokucacisa kwi-shell ye-nucleus accumbens, njengoko kulinganiswa ngenyuka kwi-concentration ye-dopamine yolwelwe kwi-dialysate efunyenwe kwi-shell ye-nucleus accumbens kunye nokunciphisa impendulo erectile eyenziwa yi-peptide injected kwiindawo ezingaphezulu kwe-hypothalamic, ezifunyenwe emva kokukhutshwa kwe-receptor ye-dopaminergic i-nucleus accumbens (jonga ngezantsi). Ngokuphathelele iinkqubo ezisebenzayo ngokuvuselela i-oxytocinergic receptors kule mimandla yengqondo, ekhokelela ekusebenziseni i-nelions ne-penile erectional eyelimbic ne-penile erection, into ecacileyo yileyo iyenzeka kwindawo ye-ventral tegmental. Ngokwenene, apha iziphumo ze-pharmacological kunye ne-immuno-fluorescence zibonisa ukuba iziphelo ze-oxytocin ezinomdla zithintela kwii-cell cells ze-dopaminergic neurons ezijolise kwi-shell ye-nucleus accumbens (Melis et al., 2007, 2009a; Succu et al., 2008). Uninzi lwezi neuron zizityebi kwi nitric oxide synthase kunye ne-guanylate cyclase. Ukuvuselelwa kwama-oxytocinergic receptors kumalungu eseli la ma-neurons e-dopaminergic kubangela ukuba kusebenze i-nitric oxide synthase ekhokelela ekuveliseni ukwanda kwe-nitric oxide production. I-oxide ye-nitric isebenzisa i-guanylate cyclase, ngokunyusa ukwanda kwe-GMP ye-cyclic, ekhokelela ekusebenziseni i-nelions i-mesolimbic ne-dopaminergic neurons kunye nokukhululwa kwe-dopamine kwi-nucleus accumbens, njengoko lilinganiswe ukwanda kwe-cellular dopamine kwi-dialysate evela kwi-nucleus accumbens etholakala yi-microdialysis ye-intra-cerebral (Succu et al., 2008 ). I-Dopamine ekhutshwe kwi-nucleus i-accumbens isebenza ngendlela evulelekileyo eya ku-penile erection. Oku kuxhaswa yikhono lokufumana i-dopamine receptor antagonist haloperidol kunye / okanye i-cis-flupentixol injected into nucleus accumbens ukunciphisa indawo ye-oxytocin eyenzelwe i-penile erection (Succu et al., 2008). Enye yeendlela ezihamba phambili ze-erectile ibonakala isebenzise i-incerto-hypothalamic ne-neoponergic neurons, ingakumbi ezo zinto zenza iifelesi zeeseloni ze-oxytocinergic neurons. Enyanisweni i-oxytocin injected kwindawo ye-caudal tegmental yandisa i-dopamine engaphezulu kwe-nucleus accumbens kodwa kwinqanaba leparagraphics, kwaye ukukhutshwa kwe-dopamine receptors kwi-nucleus ye-paraventricular kunciphisa i-oktotic-induced penile erection (Succu et al. , 2007, 2008; Melis et al., 2007, 2009a). Ubukho bale nucleus buqokelela i-dopamine-paravelricular-dopamine-paraventricular-coal-ventral tegmental indawo ye-oxtocin-dopamine Kuphakanyiswa kwakhona amandla okufumana i-apomorphine kunye ne-D4 receptor agonist PD 168077 injected in nucleus kwiphakamisi ukwenzela ukwandisa i-dopamine yamanye ama-cell kwi-shell ye-nucleus accumbens (i-Succu et al., 2007), impendulo opheliswa ngu-d (CH2) 5Tyr (Me) -Orn8-vasotocin inikwe indawo ye-ventral tegmental (Melis et al., 2009a, funda kwakhona ngezantsi). Nangona kunjalo, umsebenzi oqhubekayo kuyimfuneko ukuchonga iindlela ze-neural ezidibanisa i-nucleus ehlangene ne-incerto-hypothalamic dopaminergic system.

Indlela eyenziwa ngayo i-oxytocin yenza ukuba i-penile erection ibe esebenzayo kwaye isebenzise i-nelions ye-dopaminergic ye-mesolimbic i-neurons ye-dolaminergic xa ijojowe kwi-subiculum ye-ventral okanye kwi-posteromedial nucleus ye-amygdala iqondwa ngokucacileyo okwangoku. Kule mimandla kwakhona, i-oxytocin isebenza ngokwamkeleki ayo okukhokelela ekusebenziseni i-nitric oxide-synthase, okwandisa imveliso ye-nitric oxide. I-oksidi ye-nitric isebenza ngokucacileyo okubonakalayo okungaziwayo, okubonakala ukuba kwandise ukwenziwa kwe-glutamatergic neurotransmenti kwindawo yecala. I-Glutamic acid ivuselela i-mesolimbic ne-dopaminergic neurons ekhokelela ekuphumeni kwe-penile. Le ngcamango ixhaswa ngokukodwa ngamandla okwenza i-oxytocin injected subiculum ekwandiseni i-glutamic yamanqanaba angaphezulu kwendawo yecala (Fig. 3), kunye ne-non-competitive NMDA receptor antagonist (+) I-MK-801 injected endaweni yecala, kodwa hhayi kwi-nucleus accumbens, ukunciphisa ukunyuswa kwe-penile eyenziwa yi-oxytocin injected okanye i-subiculum ye-posteromedial ye-amygdala (uMelis et al., 2009b). Okwangoku, ezinye iinkcukacha ziyafumaneka kwi-e-ventric subiculum-induced penile erection. Nantsi i-oktocin-eyenziwe i-penile erection ibonakala yecala kwi-activation ye-oxytocinergic receptors eseziselilini ze-nitric oxide-synthase ene-neurons. Oku kubangela ukwanda kwindlela yokuvelisa i-nitric oxide, eyenza i-glutamatergic neurotransmission ngokusebenza njenge-intercellular isithunywa esinomlinganiselo ofana naloo ochazwe kwixesha elide (sibone uSnyder, 1992; uSoutham noGarbetite, 1993; Schuman and Madison, 2004) . Ngokuhambelana nale ngcamango ye-oxytocin eyenzelwe i-penile erection ivela ngokuhambelana nokunyuka kwi-extracellular glutamic acid kwi-dialysate evela kwi-subiculum ye-ventral, kunye nokuvuselela i-amino acid receptors kwi-subiculum ye-NMDA, ikhuthaza ukulungiswa kwe-penile. I-Glutamic acid yenza i-neural efference projections, ekhokelela ekusebenziseni i-nelions e-mesolimbic ne-dopaminergic endaweni ye-ventral zone, njengoko kuchazwe ngasentla. Ukuba ezi ndlela zisebenza nakwi-nucleus posteromedial ye-amygdala ayilwazi okwangoku. Ukongezelela koko, kukho ezinye iimfuno ezifunekayo ukubonisa ukuba (1) i-oxytocinergic nerve endings kunye ne-receptors kwi-subiculum ye-ventral kunye ne-posteromedial nucleus ye-amygdala ibekwe kwindawo yamaseli e-neurons aqukethe i-nitric oxide-synthase, (2) phantsi kokulawulwa kwe-amino acid (glutamatergic) kunye ne-3 ukuchonga inkqubo yokubonakalisa eyenziwe yi-nitric oxide. Kule nto, kuyaphawuleka ukuba amandla oktotocin ukwandisa umsebenzi we-nitric oxide-synthase kumaseli eseli we-dopaminergic neurons kwindawo yokuqhafaza ye-ventral kunye ne-neurons engaziwayo kwi-subiculum ye-ventral kunye ne-posteromedial nucleus ye-amygdala, ukhumbula ubuchule be-oxytocin ukwenza i-nitric oxide-synthase isebenzise kwiiselintshi ze-oxytocinergic neurons kwi-nucleus eplastiki (Melis et al., 1997). Nangona kunjalo, ngelixa ummandla wezentengiselwano owenziweyo ukwandiswa kwemveliso ye-nitric oxide kwi-cell cells ye-dopaminergic neurons ikhokelela ekusebenziseni la ma-neurons ngokusebenzisa i-guanylate cyclase kunye nokwandisa i-GMP ye-cyclic, oku akukwenzeka kwi-nucleus ephambili. Ngako oko, i-8-bromo-cyclic GMP injected kwi-nucleus yeparagraphic does not stimulate penile erection, ngelixa liyenjenjalo xa ijojowe kwindawo yecala. Enye indlela yokubonakalisa eyahlukileyo kwinkqubo ye-nitric oxidecyclic GMP ikwabandakanyeka kwinqanaba lesiphakamiso ekusebenziseni i-oxytocinergic neurons edibanisa i-penile erection nge-nitric oxide kunye / okanye exogenous nitric oxide (i-Melis ne-Argiolas, i-1995b; i-Melis et al., I-1997). . 1). Ngakolunye uhlangothi, i-GMP ye-cyclic kwiindawo ezithintekayo zibonakala zidlala indima ebalulekileyo ekusebenziseni i-nelions ye-mesolimbic ne-neurons kunye nokunyuka kwe-cellular dopamine eyenzeka kwi-dialysate efunyenwe kwigobolondo ye-nucleus i-accumulated of rats ezikhethiweyo zokubonisa okanye ukungabonisi ukungqinelani kwamapenile xa kufakwa phambi kwe-ovariectomized reception (esrogen + progesterone). Kule miqathango yokulinga, kwindoda zendoda ezibonisa ukunganyanga okungahambelaniyo, ukunyuka kwenkxalabo ye-dopamine yecala kufumaneke kulindeleke, kwaye ukwanda kwanda, nangona nje ngokuthobeka, yi-phosphodiesterase inhibitors enikezwe kwindawo ye-ventral tegmental (Sanna et al., 2009).

Ikhono le-oxytocin lijoyiwe kwindawo yendawo ye-ventral, kwi-subiculum ye-ventral kunye ne-posteromedial core cortic ye-amygdala, kunye ne-dopamine i-agonists injected into i-nucleus eparalari, ukukhuthaza ukulungiswa kwe-penile kunye nokuvuselela i-nelions i-mesolimbic ne-dopaminergic neurons. . Okokuqala, iindlela ezifana nezo zikhankanywe apha ngasentla zinokusebenza xa ukulungiswa kwe-penile kwenzeka kwiimeko zomzimba, njengokuba ngexesha lokuxubusha (xa kukho i-pulale erections) okanye ngexesha lokungahambisani ne-penile erections. Ezi zihlomelo ziyi-pheromone-mediated erections erections ezingahambelani nakwezo zonyango ngamachiza okanye i-oxytocin, eyenzekayo xa iifos ezinamandla zesondo zibekwe phambi kobuchule obungenakufikeleleka (i-estrogen + progesterone eyamkelweyo). ukuvusa (Sachs, 1997, 2007). Ewe, nangona ezi ziphumo zingabonakali ukuba i-oxytocin kule mimandla inendima ekuphakamisweni kwepenile eyenziwa kwizimo zomzimba okanye emva kokulawulwa kwezidakamizwa, bongeza amandla ngakumbi ekufunyanweni kwexesha lokuqala ukubonisa ukuba ezi ndawo zengqondo zikwazo apho i-oxytocin inikwe ukwenziwa kungekhona nje kuphela ukunyuka kweepenile izibhengezo ezibonwa emva kweziyobisi ze-erectile, kodwa kunye nokuphucula umntu (kunye nowesifazane) ukuziphatha ngokwesondo (bona u-Argiolas no-Melis, i-2004 kunye nezikhombisi apho). Ngako oko, i-oxytocin ingxube yenyuka kwi-hippocampus yamagundane angamadoda aphathwa nge-proreortile dose ye-apomorphine, i-classic dopamine agonist (i-Melis et al., I-1990) kunye ne-d (CH2) i-5Tyr (Me) -Orn8-vasotocin, ebangela i-oxytocin i-receptors, iphumelela kakhulu kungekhona nje ekuphazamiseni ukuziphatha okuphambeneyo (Argiolas et al., 1987a) kodwa kunye nomphumo wokuququzelela we-apomorphine ekuziphatheni komyeni (Argiolas et al., 1987b) kwiinkwenkwe zamadoda ezinokuziphatha ngokwesini, ngexesha apho kwenzeka. (CH2) I-5Tyr (Me) -Orn8-vasotocin nayo inamandla kakhulu ekunciphiseni ukulungiswa okungahambisani nongqingili zesondo, xa kunikwa inani le-nanogram kwiimveliso zangasemva, kodwa kungekhona kwi-PVN (Melis et al., 1999a).

Okwesibini, i-elelimbic ne-dopaminergic neurons idlala indima ephambili kwiimpawu ezikhuthazayo nezivuyisayo zokuvuselela izinto zendalo, ezifana nokutya, amanzi kunye nesondo (i-Fibiger ne-Phillips, i-1988; i-Wise ne-Rompre, i-1989; i-Everitt, i-1990). Ngokukodwa, i-dopamine ekhutshwe kwii-neuron icingelwa ukuba idibanise ukuguqulwa kwemiba ekhuthazayo yenkqubo yemvelo yokuziphatha, ngokubhekiselele kwimeko yesenzo somsebenzi wesondo, ukufuna isithandana sesini kunye nokulala ngokwesini ukufikelela umvuzo kunye nokwaneliseka (Goto noGrace, 2005). Ngenxa yoko, i-extracellular concentration ye-dopamine iyanda kwi-dialysate esuka kwi-nucleus eqokelelwa ngamagundane angamadoda okwezesondo ngexesha lokuxhamla kwi-estrogen + ye-progesterone-primed-earmed female rat, kwaye ukwanda okunjalo kwaphakama xa i-rat yindoda ivunyelwe ukuba ilandelelanise ne-female receptive (Pfaus and Everitt, 1995).

Okwesithathu, iziphumo ezikhoyo zixhasa uxhaso lokuba isiphaluka se-neural sidibanisa i-nucleus yombonakaliso kunye nommandla we-ventral ngokuthe ngqo okanye ngokungathanga ngqo (ngokusebenzisa i-subiculum ye-ventral kunye / okanye i-coreeromedial cortical nucleus ye-amygdala) kunye ne-nucleus accumbens, kwaye ukusuka apha ingaziwa ukubuyela kwakhona kwi-nucleus epalaseli ukulawula umsebenzi wee-oxytocinergic neurons ezijolise kumgca womgogodla odibanisa i-penile erection kunye ne-oxytocinergic neurons ezixhomekeke kummandla we-ventral, i-subiculum ye-ventral kunye ne-posteromedial core cortical ye-amygdala, umsebenzi we-mesolimbic ne-dopaminergic neurons (umzobo 4). Isiphaluka esisebunzima besiphaluka sinokudlala indima ekudibaniseni imisebenzi ye-neural echaphazelekayo ekulawuleni ukugqiba (erectile-ejaculatory) kunye nokulindela (ukukhuthaza nokuvuza) iinkalo zesimo sokuziphatha ngokwesini kwiimeko zomzimba. Enyanisweni, i-dopamine eyongezelelweyo isanda kwi-nucleus accumbens (i-Pfaus no-Everitt, i-1995) kunye nucleus yecala yama-rats angamadoda okwezesondo ngexesha lokungena kwi-rat ye-female receptive inaccessible. umzekelo, xa kukhishwa i-pulale errections (Melis et al., 2003). Ngaloo ndlela, nangona uphando olongezelelweyo luyimfuneko ukucacisa indima ye-oxytocin engapheliyo kwingingqi ye-ventral, i-subralulum ye-ventral kunye ne-amygdala ngexesha lokungahambelani kunye nokuziphatha ngokwesini, kungenokuba kunengqiqo ukucinga ukuba le nesekethe ye-neural hypothetical, ngelixa igalelo imiba yokuxhatshazwa kwezesondo, ngexesha elifanayo linokuphinda lisebenzise inkqubo ye-dolaminergic ye-mesolimbic yokubonelela nge-neural substrate ekuchazeni izinto ezivuyisayo zesenzo socansi (Everitt, 1990; Pfaus no-Everitt, 1995). Kulo mba, kuyaphawuleka ukuba inkqubo ye-dolaminergic ye-mesolimbic esebenze yi-oxytocin injected endaweni yendawo ye-ventral iyafana nayo isebenze ngamachiza okusetyenziswa kakubi njengama-opiates, i-cannabinoids, i-amphetamine, i-cocaine ne-alcohol (iTanda et al., I-1997) kunye ukuba i-oxytocin ifumaneka inokunciphisa ukunyamezela nokuxhomekeka kwi-cocaine, i-morphine, i-alcohol kunye ne-cannabinoids (i-Kovacs et al., i-1998; iCui et al., i-2001). Ekugqibeleni, kubonakala sengathi i-oxytocin ayikhululwanga kuphela kwindawo ye-ventral, kodwa nakwi-subiculum ye-ventral kunye ne-posteromedialucletic nucleus ye-amygdala, inokuvula i-nelions eye-dolaminergic neurons, engabandakanyeka kwimpembelelo enomdla kunye nembuyekezo yokusebenza ngokwesondo . Ukusebenza kwe-nelions i-mesolimbic ne-dopaminergic i-neurons ingaba ngqo, ngokufumana i-oxytocinergic receptors kumalungu eseli e-mesolimbic ne-neoponergic neurons, okanye ngokungathanga ngqo ngokusetyenziswa kwe-glutamic acid neurotransmission kwindawo ye-ventral.

I-Dopamine ekhutshwe kwi-nucleus accumbens igobolondo ihlengahlengisa umsebenzi we-incerto-hypothalamic neoponergic neurons kwi-nucleus eparaseli eyenza i-penile erection (ngokusebenzisa i-oxytocinergic neurons eyenza i-spinal cord), okanye isishukumiso sezesondo kunye nomvuzo (ngokusebenzisa i-oxytocinergic i-neurons eyenza indawo ye-ventral tegmental, i-subiculum ye-ventral okanye i-coreeromedial cortical nucleus ye-amygdala). Ekubeni i-dopamine iphinda ikhutshwe kwi-nucleus iqokelele igobolondo kunye ne-nucleus epalastiki xa i-penile erection ivela kwiimeko zomzimba (umzekelo, ukungasebenzi okungahambisani nokulandelana) (Succu et al., 2007; i-Melis et al., 2003, 2007), mhlawumbi ukuba i-oxytocinergic neurons ebandakanyekayo ithatha inxaxheba kwizijikelezo ze-neural zidibanisa ukusebenzisana phakathi kwe-mesolimbic kunye ne-incerto-hypothalamic dopaminergic system. Ezi zijikelezo ze-neural zingadlala indima kungekuphela kwisigaba sokuphela kwesenzo sokuziphatha ngokwesondo (umzekelo, ukulungiswa kwepenile kunye nokuxubusha), kodwa nangenxa yezizathu zesini, ukuvuswa kwesondo kunye nomvuzo wesini.

Umzobo 4.

Ukumelwa kweSikimenti yesiphaluka se-neural esichaphazelekayo echaphazela i-oxytocin echaphazela ukukhuthazwa ngokwesondo, ukuvuza kunye nokusebenza ngokwesondo, njengoko kucetyiswa ziziphumo zale sahluko kunye neengxelo zangaphambili. I-oxytocinergic neurons ezivela kwinucleus yecalastiki kunye neprojekthi yecala lomgudu xa iqhutywe ngumbono we-dopamine kunye ne-glutamic acid (kodwa nakwezinye i-neurotransmitters kunye / okanye i-neuropeptides), ukuququzelela ukulungiswa kwe-penile kunye nokusebenza ngokwesondo ngokusebenzisa i-oxytocinergic neurons eyenza umgca wesipelini. I-Dopamine kunye ne-glutamic acid (kodwa kunye neurotransmitters kunye neuropeptides) kwi-nucleus yeparagraphicic ibuye isebenze i-oxytocinergic neurons eyenza indawo ye-ventral tegmental, ngaleyo ndlela isebenzise i-nelions ene-dolaminergic neurons eyenza i-nucleus accumbens, ukulungelelanisa izizathu zesini kunye nomvuzo. I-Dopamine ekhutshwe kwi-nucleus accumbens (NAs) isebenza ngokuqhubekayo engazange yaziwa ngeendlela ze-neural, ezandisa ukwenziwa kwe-incerto-hypothalamic neoponergic neurons (ezivela kumaqela a-A13-A14 aseDahlstrom kunye neFuxe) aphethwe yi-neurosic oxycycinergic, kuquka ezo intambo yomgogodla, ekhokelela ekuphumeni kwepenile. Le isiphaluka ingasetyenziswa kwakhona yi-oxytocin injected hhayi kuphela kwindawo ye-ventral tegmental, kodwa nakwi-subiculum ye-ventral kunye ne-amygdala, efumana i-oxytocinergic yokungabikho kwi-nucleus ephambili, mhlawumbi ngokugqithisileyo okanye ngokungaqhelekanga kwe-glutamatergic. indawo ehamba phambili, ekhokelela ekumodulweni kokushukunyiswa kwesondo kunye nokulungiswa kwe-penile. Ekugqibeleni, isiphaluli esingentla singasetyenziselwa iifomula kunye ne-pheromones, ekubeni i-dopamine yeselula kunye nokwanda kwe-acutamic acid kwi-nucleus yeparagraphic (kunye nakwiindawo eziphambili ze-preoptic) ngexesha le-pheromone-interactive-interactive-interact actions and copulation Uludwe lweenkcukacha).

Ukubonga Lo msebenzi uncediswa ngokuxhaswa yigranti evela kwiNkonzo yaseNtaliyane yeYunivesithi kunye noPhando ku-AA no-MRM

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