I-Lateral Hypothalamic Serotonin Inhibits I-Nucleus Accumbens Dopamine: Impembelelo yokuxhatshazwa ngokwesondo (1999)

I-Journal ye-Neuroscience, I-1 kaSeptemba 1999, 19(17): 7648-7652;


UDaniel S. Lorrain, UJon V. Riolo, Leslie Matuszewich, yaye Elaine M. Hull

+ UkuBambisana noMbhali

  1. 1 ISebe lezeengqondo, iYunivesithi yaseNew York e-Buffalo, Buffalo, New York 14260
 

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Abstract

I-Dopamine (DA) ikhutshwe kwiindawo ezahlukeneyo zobuchopho, kubandakanya ne-nucleus accumbens (NAcc), ngaphambi nangexesha lokulinganisa kwiirowu zesilisa. I-agonists ye-DA elawulwa kule ndawo iququzelela, kwaye abachasi be-DA banqanda, iindlela ezininzi zokuziphatha eziqinisekileyo, kubandakanya nokuziphatha ngokwesondo kwamadoda. I-Serotonin (5-HT) ngokubanzi inhibitory ekuziphatheni ngokwesini kwamadoda. Sabika ngaphambili ukuba i-5-HT ikhutshwe kwindawo ye-anterior lateral hypothalamic (LHAA) kwaye nokuba i-serotonin ekhethiweyo iphinde inhibitor inhibitor ifakwe kwindawo leyo ilibazisekile kwaye icothise ukunyanzelwa. Iziphumo zethu zangoku, zisebenzisa i-micodialysis ephezulu ye-temporal resolution, (1) iqinisekisa ubungqina be-electrochemical yangaphambili yokuba amanqanaba e-extracellular okwanda kwe-DA kwi-NAcc ngexesha lokushicilela kunye nokuhla ngexesha lokuphumla kwe-postejaculatory (PEI) kunye (2) kudiza ukuba i-LHAA I-5-HT inokuthintela ukukhutshwa kwe-basal kunye ne-elicised DA ukukhutshwa kwi-NAcc. Ezi ziphumo zibonisa ukuba umjikelezo we-neural wokukhuthaza i-quiescence yesondo ngexesha le-PEI ubandakanya ukufakwa kwe-serotonergic kwi-LHAA, yona ithintela ukukhutshwa kwe-DA kwi-NAcc. Ezi ziphumo zinokubonelela ngokuqonda malunga nolawulo lwe-inhibitory lwezinye iindlela zokuziphatha ezivuselelweyo eziqhutywa yi-NAcc kwaye zinokubaluleka kokuqonda imiphumo yesondo exhaphakileyo kumayeza e-antidepressant.

Ukuziphatha ngokwesondo kwabantu abesilisa, i-non-man eximates, kunye neentonga ziphenjelelwa yi-dopamine (DA) kunye ne-serotonin (5-HT) neurotransmission (IBitran kunye neHull, 1987; UGorzalka et al., 1990; I-Zajecka et al., 1991; IMeston kunye neGorzalka, 1992; I-Wilson, i-1994; UMelis noArgiolas, 1995). Ngokubanzi, i-DA iyonyusa, ngelixa i-5-HT inhibits, inkuthazo yesini kunye nokusebenza kwaye ke kunganegalelo ekuqaliseni nasekuthandeni, ngokulandelanayo.

Kukho ubukho besikhuthazo esifanelekileyo sesondo, i-DA yangaphandle yanda kwii-nucleus accumbens (NAcc) (Mas et al., 1990; Pfaus et al., 1990; Damsma et al., 1992; Fiorino et al., 1997kunye nendawo ye-medial preoptic (MPOA) (Hull et al., 1995) zeempuku zesilisa; Amanqanaba e-DA enyuka ngakumbi ngexesha lokushicilela. I-DA ihlala iphakanyisiwe de i-male male ibuye, emva koko kunciphe amanqanaba e-DA (Blackburn et al., 1992). Emva kwesithuba sekhefu (i-PEI) lokuvuselela ngokwesondo, ikopi iyaqala kwaye ifaniswe nokukhululwa kwe-DA. Le patheni incede ekuchazeni indima kwi-DA ekuququzeleleni isimilo samadoda. Nangona kunjalo, izinto ezinqanda ukukhutshwa kwe-DA emva kokuba i-ejaculation (kwaye ngenxa yoko inokuba negalelo kwi-PEI) ifumene ingqwalaselo encinci.

I-Serotonin ngokubanzi inqanda ukukopishwa. Ukuziphatha ngokwesondo kukhubazeka ngama-agonists amaninzi e-5-HT kunye neearhente ezikhulisa ukubakho kwe-5-HT kwaye kuququzelelwa zizilonda ze-serotonergic kunye nabachasi abaninzi be-receptor (IBitran kunye neHull, 1987; UGorzalka et al., 1990; I-Wilson, i-1994). Oluvavanyo lukhuthaza i-hypothesis ukuba i-5-HT ye-endoo ikhutshwe kwi-ejaculation kwaye inokulawula i-PEI. Ex vivo amanqanaba e-tishu yangaphambi kwexesha ye-5-HT (Mas et al., 1987) Kunye kwi vivoinyathelo lokuqala le-microsalysate ye-5-hydroxyindoleacetic acid [eyona metabolite ephambili ye-5-HT (Fumero et al., 1994)] yanda kakhulu kuphela emva kwembonakalo. Ke, i-5-HT inokukhutshwa kwimimandla yesiphelo ye-serotonergic, kubandakanya indawo yendawo ephambili, kunye nokukhuthaza ukungahambelani ngokwesondo ngexesha le-PEI. Kutshanje siye silinganisa i-5-HT ye-extracellular kwi-MPOA kodwa asifumananga zinguqu ngexesha lokuprinta okanye emva kokubhengeza (Lorrain et al., 1997). I-extracellular 5-HT yenze, nangona kunjalo, yanda kwindawo engaphandle ye-anterior yendawo ye-hypothalamic (LHAA) ngokukhawuleza emva kokuba I-5-HT kwi-LHAA emva koko yancitshiswa yaya kumanqanaba osiseko ngaphambi kokuphinda iqalise ukusebenza. Ngaphaya koko, i-microinjection ye-serotonin ekhethiweyo yokubuyisela kwakhona inhibitor (i-SSRI) kwi-LHAA Ukulibaziseka kokuqala kokukopishwa (ngokufanayo ne-PEI) kunye nokulibaziseka kwi-ejaculation emva kokuba indoda iphinde yaqhuba ukukopisha (Lorrain et al., 1997). Ngokucacileyo, ukukhutshwa kwe-5-HT kwi-LHAA Inhibitory kukopisho kwaye inokuba negalelo kwi-PEI.

Ukuqikelelwa kwe-5-HT okuvela kumqolo kungacinezela iinkqubo ze-catecholaminergic ye-forebrain.I-Yamamoto kunye ne-Ueki, i-1978). I-LHAA ifumana igalelo le-5-HT ukusuka kumgaqo (Ukuhluma et al., 1982; I-Vertes, 1991) kunye negalelo leentsinga ezisebenzayo ezinyukayo okanye zehla ngentloko yentsimbi yangaphambili (Umthengisi et al., 1979;Hakan et al., 1992). Sivavanye ukuba ingaba i-5-HT ikhutshwe kwi-LHAA inokuwucinezela umsebenzi wokwabelana ngesondo ngokuthintela inkqubo ye -accaccumbens ye-DA. Kwiinzame ze-1 sisebenzise i-Microdialysis ukuqinisekisa idatha yangaphambili ye-electrochemical ebonisa ukwanda kokukhutshwa kwe-NAcc DA ngexesha lokukhuphela kunye nokunciphisa ukukhutshwa emva kwe-ejaculation. Kwilinge 2, silungiselele i-5-HT kwi-LHAAngokubuyisela umva ngokuchwetheza kunye nokuvavanya ngaxeshanye ifuthe lazo ekwenziweni kwe-basal nakwi-NAC kwi-DA ekhulayo.

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IMPAHLA NENKQUBO

I zifundo. Iirandi zeshumi elinesihlanu zesini ezinamava ziye zahlaliswa ngokukodwa kwizikhephe zeplastiki kwaye zigcinwa kumjikelezo wokukhanya okubuyayo / omnyama kufakwe izibane kwi-11: 00 AM nakwi-10: 00 PM Ukutya namanzi bekufumaneka ad adum. Ukuvavanywa kwe-1, izifundo ze-7 zifumene i-cannula yesikhokelo esingaxutywanga ejolise kumhlaba weqokobhe le-NAcc [anteroposterior, + 3.0; i-Mediolateral, + 1.0; kunye dorsoventral, −5.2 (I-Pellegrino et al., 1979)]; Izifundo ezisele ze-12, esetyenziselwa kulingo 2, ukongeza wafumana i-ipsilateral guide cannula ejolise kwi-LHAA[i-anteroposterior, + 1.3; i-Mediolateral, + 1.5; kunye dorsoventral, −7.2 (I-Pellegrino et al., 1979)]. Emva kwexesha leveki ye-1 yokubuyisela kwimeko yesiqhelo, iiseshoni ze-micodialysis zaqala. Zonke iinkqubo zilandela izikhokelo kwaye zamkelwa yiKomiti yokuNakekelwa kweZilwanyana yaseKhaya kunye neKomiti yokuSetyenziswa.

Unyango. I-Concentric micodialysis probes yenziwa elebhu. Ngokufutshane, ityhubhu yensimbi engenasici ye-27 ga yaze yafakwa dialysis membrane [12,000 kDa cutoff; I-210 μm ububanzi obungaphandle (od); I-1 mm indawo esebenzayo-yokuhombisa; I-Spectra Por, i-Houston, TX] kwelinye icala kunye nesiqingatha se-3 cm ye-polyethylene 20 tubing kwelinye icala ukuze isebenze njengesiqwengana sendlela yokuhanjiswa. Isiqwenga se20 cm se-silica capillary tubing [125 μm od; I-50 μm ububanzi obungaphakathi (id); I-Polymicro Technologies, i-Phoenix, AZ], yanisongelwe ezantsi kwi-dialysis tube, yasebenza njengendawo yokuphuma. Ukulinga i-1, umyinge wokuhamba kwidayalysate yayiyi-1 μl / min; iisampulu zaqokelelwa yonke i-3 ye-min kwiibhubhu ze-microcentrifuge (250 μl), ibekwe kumkhenkce owomileyo, kwaye yafakwa ngaphakathi kwe-1 hr kwikholam ye-capillary yokuhlaziywa koxinaniso lwe-DA yi-HPLC ngokufunyanwa kwe-electrochemical (HPLC-EC). Ukuvavanywa kwe-2, umyinge wokuhamba kwidayalysate yayiyi-0.5 μl / imiz, kwaye iisampulu zaqokelelwa rhoqo kwimizuzu ye-10. Kuzo zombini iimvavanyo, i-dialysis perfusion medium yayisisombululo sikaRinger esisisombululo esine-138 mm I-NaCl, i-2.7 mm I-KCl, kunye ne-1.2 mm CaCl2, pH 7.0. Ukuhamba kwakulawulwa yipompo yokufaka inaliti yeHarvard (imodeli ye-22; iCambridge, MA). Kwintsasa nganye nganye yeseshoni yokuhanjiswa kwentsholongwane, izifundo zafakwa ixeshana kancinci nge-ether ukuvumela ukufakwa kweprobiyo (ii) protenialysis. Ukuhamba kwe dialysate kwaqala kwangoko, kwaye ixesha lokuzinza le-5 hr lavunyelwa ngaphambi kokuqokelelwa kwesampula. Yonke idatha yokuvavanya i-Microdialysis ihanjiswa njengepesenti yesiseko [esekwe ngokuthatha i-avareji yeememorandi ezintathu ezilandelelanayo (isilingo 1) okanye iisampulu ze-predrug (experiment 2).

I-HPLC. Ukufunyanwa kwe-DA kwagqitywa kusetyenziswa i-HPLC-EC ye-capillary. Isampulu nganye yalayishwa ngesandla kwi-valve ye-injini ye-VALCO eyenzekelayo, ihambisa i-500 nl kwikholam ye-C18 reverse-phase capillary column (0.3 mm id × 5.0 cm; 3 μm sphere; LC Packings, San Francisco, CA). Isigaba sokuhambisa esine-30 mm i-citric acid, i-50 mm isodium acetate, 0.027 mmNa2I-EDTA, kunye ne-0.25 mm I-octyl sodium sulfate, ene-2.5% acetonitrile kunye ne-0.2% tetrahydrofuran (v / v), pH 3.6, kwaye yathunyelwa isebenzisa imodeli ye-Gilson, Inc. (Middleton, WI) 307 isebenza kwi-0.5 ml / min kwaye ixhotywe yiAquurate flow. isiqhekeza (iipakethi ze-LC). Isiphazamisi sokuhamba kokuhamba siye sanikezela i-6 /l / i-min yesigaba sesoftware engenasiphulelo kwikholamu yohlalutyo. I-Dopamine oxidation ifunyenwe kusetyenziswa umlawuli we-Antec DECADE (Leiden, The Netherlands) esebenzisa iseli elihambahamba elincinci (umthamo we-11 nl ivolumu) eneglasi yecarbon yegesi ekhawulezayo egcinwe kwindawo enokusetyenziswa njenge- + 0.7 V isihlobo kwi-electrode ye-Ag / AgCl. Inkqubo ibibalwa imihla ngemihla ngenqanaba le-DA elisanda kulungiswa kwi-1 pg / μl (0.5 pg kwikholam).

Inkqubo. Kwiinzame ze-1, emva kwexesha lokuzinza le-5 hr kwaye emva kokuqokelelwa kweesampulu zesiseko sokudayala, kwabakho owasetyhini ozimeleyo kwibala lokuvavanywa kwindoda, kwaye kwaqala ukwenziwa. Indoda yayivunyelwe ukuba ikhuphele ukuya kutsho kwimitha ezintathu. Ngeli xesha, iisampulu zaqokelelwa kwi-3 min bins kunye zaza zafakwa iilebhile njengoko ezo zaqokelelwa ngexesha lokushicilela (i-COP) kunye nezo zaqokelelwa ngexesha lokungabelani ngesondo emva kokuba kuye kwakho (i-PEI). Amaqela amathathu eesampulu (ngokusekwe ekuziphatheni kwendoda ngexesha lokuqokelelwa) asekwa ngokohlalutyo olulandelayo lwe-HPLC lwesiqulatho se-DA: isiseko (BL), COP, ne-PEI.

Kwiinzame ze-2, emva kwexesha lokuzinza le-5 hr kwaye emva kokuqokelelwa kweesampulu ezisisiseko ngenkqubo ye-micodialysis ekwi-NAcc, ukugeleza kwaqalwa kwiprojekti ese-ipsilateral LHAA, ehambise nokuba yi-5-HT [1 mg / ml (5.6 mm); I-Sigma, iSt. Louis, MO] okanye imoto (isisombululo sikaRinger). Iisampulu zokudayela ziyaqhubeka nokuqokelelwa kwi-NAcc kwimigodi ye-10 min ngexesha le-40 min ye-LHAA ukufakwa. Ukuvavanya uxinzelelo lwe-5-HT yokukhutshwa kokukhutshwa kwe-NAcc ye-DA, sabeka ibhinqa elilinganayo kwindawo yovavanyo yamadoda ngexesha lokuqokelela isampulu yokugqibela, ngaxeshanye ne-LHAA I-5-HT i-perfusion (okt, ixesha, i-30-40 min emva kwesiseko). Yonke into eyindoda ibonakalisa ezinye iindlela zokuziphatha ngokwesondo; nangona kunjalo, ukusebenza kwabo akubanga manqaku.

Histology. Emva kweseshoni ye-Microsalalization, izilwanyana zazingafakwanga kakuhle ngepentobarbital yesodium, kwaye idayi yecresyl ye-cresyl yenziwa yafumaneka kwi (pro) ye-micodialysis. Izihloko emva koko zachazwa, kwaye iingqondo zazo zasuswa ukuze kuqinisekiswe ukubekwa endaweni yophando. Zezo zilwanyana kuphela ezinedayi eluhlaza okwesibhakabhaka kwingingqi ye-Nacc (ukulingwa kwe-1) kunye ne-LHAA(uvavanyo lwe-2) lwalusetyenziselwa uhlalutyo lweenkcukacha manani.

Uhlalutyo lwedatha. Ukuvavanywa kwe-1, njengoko kuchaziwe apha ngasentla, idayali eqokelelwe kwi-NAcc yahlulwahlulwahlulwahlulwahlulwahlulwahlulwahlulwahlulwahlulwa kathathu kwiindlela zokuziphatha: I-BL, i-COP, ne-PeI (eboniswe njengeepesenti). I-ANOVA yendlela enye yayiqhutywa kwiipesenti ze-DA zala maqela mathathu. Kungenxa yokuba uvavanyo lokuvavanywa ngokufanayop <0.001), i-ANOVA yeKruskal-Wallis yendlela enye yenziwa kwinqanaba, ilandelwa nguiposi uthelekisa usebenzisa indlela kaDunn. Ukuvavanya i-2, kwasetyenziswa iindlela ezimbini eziphindaphindiweyo i-ANOVA, kunye ne-perfusate (5-HT vs imoto) njengento ephakathi kwezinto kunye nexesha (i-6 okanye i-10 min dialysis bins) njengeyona nto ingaphakathi, kuvavanywa iziphumo ze-5-HT ukufakwa kwi-LHAA kumanqanaba e-NAcc DA.Post post Ukuthelekisa iScheffé kwenziwa ngokweIKirk (1968).

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IINKCUKACHA

I-1 yesilingo: Ukukhutshwa kwe-DA kwi-NAcc ngexesha lokukhuphela kunye nasemva kwe-ejaculation

Ukukhutshwa kwe-DA kwi-NAcc kulandele ipatheni ebonisa ukuqalisa kwendima yokusebenza kwale neurotransmitter. Ipateni eqhelekileyo yesilwanyana ngasinye inokubonwa kuMzobo1 A; Ukukhutshwa kwe-DA kwakuphezulu ngexesha lokukhuphela kodwa kwehla emva kwe-ejaculation nganye (okt, ngexesha le-PEI). I-ANOVA kumanqanaba edatha yamaqela ichaze umahluko obonakalayo kumanqanaba e-daalysate e-DA kuwo onke amabakala okuziphatha [H(2) = 14.794; p <0.001; Umzobo 1 B]. Post post uthelekiso lubonise ukuba i-DA yayiphezulu kakhulu kwiisampulu eziqokelelweyo ngexesha lokushicilela, ngokuthelekiswa nezo zaqokelelwa ngexesha le-BL okanye le-PEI (p <0.05).

Umzobo 1.

Jonga inguqu enkulu:

Umzobo 1.

In vivo Ukukhutshwa kwemibhobho yokukhutshwa kwe-DA kwi-NAcc yamagundane angamadoda ngexesha leseshoni yokuziphatha.A, Umzekelo omele utshintsho lwexeshana kumgangatho omnye. B, Ukutshintsha kotshintsho kukukhutshwa kwe-DA (± SEM) yeqela lamagundulu amathandathu. Iisampulu zaqokelelwa kwizithuba zemizuzu eyi-3 ngexesha lokuthathelwa kochungechunge lwendlela ezintathu kwaye zonyulelwe ukumiselwa kwangaphambili kwe-BL (izangqa ezizele), COP (iindidi ezivulekile), okanye iPII (isangqa esirhangqiweyo). Umxholo we-Dopamine wawumkhulu kakhulu kwiisampulu eziqokelelwe ngexesha lokukhuphela, uthelekiso kunye neesampulu eziqokelelweyo phantsi kweemeko ze-BL kunye ne-PEI (**p <0.05).

Uvavanyo lwe-2: Iziphumo ze-5-HT kwi-LHAA kwi-DA kwi-NAcc

Ukubuyela umva kwe-5-HT kwi-LHAAkunciphise ukukhutshwa kwesiseko kwe-NAcc DA kunye nokuthintela ukukhutshwa okuphuculweyo okuqhele ukubonwa ngexesha lokuprinta (Fig.2). I-ANOVA eqhutywa kwezi datha ichonge ifuthe lamaqela [F (1,10) = 46.324; p<0.001] nexesha [F (5,50) = 11.232; p <0.001] kunye neqela x ixesha lokudibana [F (5,50) = 22.876;p <0.001]. Post post ukuthelekisa kutyhila ukuba i-DA yayisezantsi kakhulu kwisampulu nganye yeesampulu ezine zeedayilini kuqokelelwa ngexesha le-5-HT, xa kuthelekiswa namaxabiso asisiseko (p <0.05). Izilwanyana ezifumana isithuthi kwi-LHAA kubonise ukonyuka okukhulu kwi-NAcc ye-DA kwisiseko (p <0.05) ngexesha lokulingisa; Nangona kunjalo, akukho lonyuselo luqwalaselweyo kwizilwanyana ezifumana i-5-HT kwi-LHAA.

Umzobo 2.

Jonga inguqu enkulu:

Umzobo 2.

Utshintsho lwexeshana kwiDA luxinzelelo lwe dialysate eqokelelwe kwi-NAcc ngaphambili nangexesha le-40 min ye-5-HT ukufakwa kwi-LHAA kwiirhasi eziyisithupha zamadoda. Iisampulu zaqokelelwa kwizithuba zemizuzu ye10. Ibhinqa elingumfazi laziswa kwindoda, kwaye ikopi yavunyelwa ngexesha lokuqokelela isampulu yokugqibela ngexesha le-5-HT yokuhanjiswa. Ukwehla okukhulu kwi-DA kwenzeka ngalo lonke ixesha le-5-HT. Olu nyango luvimbele ukunyuka kokukhululwa kwe-NAcc DA kubonwe kwizilwanyana ezilawulayo [*p <0.05, amaxesha e-perfusion vs ixesha 0 (isiseko)]. VEH, Isithuthi.

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UKUQALA

Ezi ziphumo zibonisa unxibelelwano lwe-neurochemical phakathi kweenkqubo ze-hypothalamic kunye ne-mesolimbic yeengqondo ezinokukhuthaza i-quiescence ngokwesondo ngexesha le-PEI. Kwiinzame ze-1 saseka ukuba amanqanaba e-extracellular e-DA enyuka kwi-NAcc yamagundwane angamadoda ngexesha lokukhuphela kodwa ke anciphe emva kwe-ejaculation, ngexesha le-PEI. Iziphumo ezifanayo ziye zachazwa, ngokusekwe kwi vivoIindlela zobuchule be chronoamperometric (Phillips et al., 1991). Nangona ubuchwephesha obunjalo bunesisombululo esiphezulu sokwexeshana, abanakukwazi ukwahlula ngokupheleleyo iminikelo ye-DOPAC kunye ne-ascorbic acid ukusuka kuleyo yeDA ukuya kumqondiso (I-Dayton et al., 1981; Gonon et al., 1984). Mva nje, ukusebenzisa kwi vivo Ukuvavanywa kwe-micodial, enesisombululo esihle kakhulu se-neurochemical, UFiorino et al. (1997) ukugqiba kwelokuba ukwahluka ngokwesondo kunokuba nokuhambelana nokungakwazi komfazi obhinqileyo ukukhuthaza ukunyuka kwamanqanaba e-NAcc e-DA. Kweso silingo isampulu ye-15 ye-sampling yasetyenziswa, ukuthintela inkcazo yokulandelelana komntu ngamnye. Olu vavanyo lwangoku lusebenzise ixesha lokuguqula isampulu ye-3, ukubonelela okokuqala kwisisombululo esiphezulu seetemplate kunye nokusonjululwa kwe-neurochemical kuhlalutyo oluhlaziyiweyo lokukhululwa kwe-DA ngexesha leziganeko ezithile zokuziphatha. Ukuphuculwa kokukhutshwa kwe-NAcc DA ngexesha lokukhuphela kwakungagcinwanga kuyo yonke i-PEI. Oku kuphakamisa ukuba iipropathi ezonyusayo ze-DA zowasetyhini we-estrous zenziwa ngococeko okanye zithintelwe kwangoko emva kokumiswa.

Amanqanaba e-hypothalamic ye-5-HT ye-lateral, eyonyuka emva kwe-ejaculation, inokuba negalelo kwi-quiescence yesini ye-PEI. Ukulawula i-5-HT kwi-LHAA ngokubuyisela umva ngokuchwetheza kwilinge lokuvavanya i-2, kufana ne-ejaculation, kwavelisa ukuncipha kwangoko kwamanqanaba angaphandle kwe-DA kwi-NAcc. I-Dopamine iyaqhubeka nokuhla ngokuthe chu kulawulo lonke lwe-5-HT. Olu nyango luthintele ukonyuka kwe-DA yabasetyhini ebakhenkethi eqhelekileyo enxulunyaniswa nokukhuphela.

Sixele kutshanje ukuba i-5-HT ye-extracellular inyuke kwi-LHAA emva kwe-ejaculation; I-microinjection ye-SSRI kulo mmandla ilibazisile ukuqala kwesondo (ngokufanayo ne-PEI) kwaye yalibazisa ukulumkiswa emva kokuqala kokuprinta kodwa ayizange iphazamisane nokubuzwa ngokubanzi (Lorrain et al., 1997). Ezi datha, kunye nezinto ezifunyaniswayo ngoku, zicebisa ukuba ukumiswa okungxamisekileyo kopopayi emva kokuba kuyekwe, kungenzeka, kulawulwe ngokukhutshwa kwe5-HT kwi-LHAA kunye nesithintelo esikhokelela kwi-mesoaccumbens DA. Ngaphantsi kweemeko eziqhelekileyo, i-DA ikhutshwa ngaphakathi kwe-NAcc yeerhasi zamadoda xa ikhoyo i-estrous cuesLouilot et al., 1991; Damsma et al., 1992). Lo mbutho we-DA unokuvula owesilisa ukuba ahambisane nowasetyhini. Izilonda ezihluthayo ze-DA ze-NAcc zinciphise inani lezinto zokwakha eziguqukayo xa kuphendulwa kwisimo esikude ukusuka kumfazi othembekileyo kunye nokulibazisa ukuqala kokopelo (Liu et al., 1998). Ngexesha le-PEI, i-NAcc DA yamanqanaba iyancipha (ulingelo lwe-1), njengoko kusenziwa kuboniso lwenkqubela phambili yesondo kowasetyhini. Ukunyuka kwe-5-HT kwi-LHAA inokuba yinto ebalulekileyo ekuthinteleni iinkqubo ze-neuronal ezihlala zenza i-mesoaccumbens ye-DA kunye nokuziphatha okungathandekiyo.

Ulawulo lwe-inhibitory malunga nokukhuphela ngexesha le-PEI yinto ebalulekileyo kwimpumelelo yokuzala. Ukuqala kwangoko kobupopayi kungashenxisa iplagi yesidoda esikhuthaza ukuhambisa isidoda kwisibeleko sowasetyhini (Umthengisi kunye neZoloth, 1970; I-Sachs, 1982); Ngaphaya koko, i-ejaculate yesibini eyenzeka ngokukhawuleza emva kokuba eyokuqala inokuba nesidoda esimbalwa kunangaphambili. I-quiescence yesondo ye-PEI ayisosiphumo sokusilela kwe-erectile; Iimpawu ezibonakalayo ezigciniweyo zigcinwa, okanye ngokwenene ziphuculwe, yi-ejaculation yangaphambili (I-O'Hanlon kunye ne-Sachs, 1980). Ke ngoko, kubalulekile ukuba ubudoda (kunye nomntu obhinqileyo) buthinteleke ngexesha le-PEI ukukhuthaza ukukhulelwa okuphumelelayo. Ukwehla ngokufanayo kwe-LHAA I-5-HT (Lorrain et al., 1997) kunye nokonyuka kwe-NAcc DA ekupheleni kwe-PEI iphakamisa indlela yexesha lokuxoka kwezesondo. Ukuqwalaselwa kweenkqubo ezimbini ezihambelanayo azisiyisi sikhombisi sokuzala. Nangona kunjalo, ukufumana ukuba ukuphinda kuchwe kabini kwe-5-HT kwi-LHAA kunciphisa amanqanaba e-extracellular ye-DA kwi-NAcc iphakamisa ukuba ukunyuka kwe-postejaculatory kwi-5-HT kwi-LHAA iqhele ukubangela ukwehla kwe-NAcc DA.

I-LHAA inokulungelwa ngokufanelekileyo ukumodareyitha ulwazi oluhambelana nezesondo ukusuka kwi-hypothalamus ukuya kwingqondo iphela. Umda we-hypothalamus uye wachazwa njengolawula indlela yokuziphatha kunye nokuvuselela (I-Benarroch, 1993). Ii-neurons ezininzi kwi-lateral hypothalamus (LH) zitshintshe ngokukhawuleza amazinga abo okudubula ekuphenduleni kwizitofu ze-testosterone okanye ye-estrogen (I-Orsini, 1982) kunye nokulawula usetyenziso lwalo mahomoni (I-Orsini, 1985). Ngapha koko, uhlalutyo lwe-2-deoxyglucose e-semiquantitative ye-neural activation yveza ukwanda komsebenzi we-neural kwi-LH ekuphenduleni ivumba labasetyhini (I-Orsini et al., 1985). Ke ngoko, ii-neurons ze-LH zinokukhuthaza umdla wesini sowesilisa kunye / okanye umsebenzi. Ukongeza, ukusikeka kwe-parasagittal ukwahlula i-MPOA kwi-LHAA/ / - /ISzechtman et al., 1978; IBrackett kunye neMva, 1984).

Zimbalwa iindlela ezinokubakho zendlela ezinokuthi zilamle i-LHAA I-5-HT inefuthe ekukhutshweni kwe-NAcc DA (Fig.3). I-LHA ibandakanyiwe kwiqela lezakhiwo ezibandakanya indawo esembindini, ebonakalisiweyo ukuba inonxibelelwano olubuyisanayo kunye ne-NAcc (Hakan et al., 1992; Wu et al., 1996). Kukho nobungqina obuvela kwindledlana yendlela ehla ukusuka kwi-LH ukuya kwindawo yecutralal disc (VTA) (I-Wolf kunye ne-Sutin, i-1966; Umthengisi et al., 1979). Ke ngoko, ukukhutshwa kwe-DA kwi-NAcc kunokuphembelela ngokuthe ngqo kwindlela enyuka kwi-LHA iye kwi-NAcc okanye ngendlela engalunganga ngendlela yokuhla ukusuka kwi-LHA iye kwi-VTA.

Umzobo 3.

Jonga inguqu enkulu:

Umzobo 3.

Ukumelwa kwesikimu kwemijikelezo ye-neural enokwenzeka ebandakanyeka kwi-LHAA I-5-HT inhibition ye-NAcc DA yokukhutshwa. Ukukhutshwa kwe-DA kunokuba nefuthe kwi-5-HT ebambela ngokuthe ngqo kwi-LHAA kwi-NAcc (A) okanye i-neurons yendlela yokuqikelela engathanga ngqo ekufikelelwa kwi-VTA (B). Ihlulwe kwi I-Paxinos ne-Watson (1982). I-MFB, isiqwenga sokwenyama sonyango lweMedical.

Intsimi ye-terminal ye-NAcc yenziwa ngamacandelwana amabini aphambili, iqokobhe kunye nomxholo (wokuhlaziya, bona UDeutch et al., 1993). Kwisifundo esikhoyo, ukubekwa kwezinto zokuvavanya i-micodialysis bekukhawulelwe kwigobolondo kwaye ke kubonakalisa i-LHAA Ukulawulwa kwe-5-HT kolu hlolo. Akukaziwa ukuba isiseko sidibaniswe ngokufanayo na. Olu lwazi lunokunika ukuqonda ngumahluko phakathi kwezi ziqendwana zibini kulawulo lweendlela zokuziphatha ezishukumisayo.

Nangona ikopi ayifumananga mpendulo ye-DA kwi-NAcc ipsilateral kwi-5-HT reverse dialysis (ukulingwa kwe-2), onke amadoda abenakho ukulingisa, mhlawumbi ngenxa yomsebenzi oqhelekileyo we-DA kwisivumelwano esingafikeleliyo secandelo. Iiparamitha zokuziphatha zazingarekhodwa, ngoko akunakwenzeka ukwazi ukuba ingaba izilwanyana ze5-HT zahlukile kulawulo. Nangona kunjalo, ii-microinjection ezimbini ze-SSRI kwi-LHAA Ulibazisile kwaye ucothise ukuthelekisa kulingo lwangaphambili (Lorrain et al., 1997). Izilonda ezihluthayo ze-DA ze-NAcc ziye zalibazisa ukuqala kwepolisi (Liu et al., 1998), kunye nokunciphisa ukukhutshwa kwe-NAcc DA ukulibaziseka kunye nokucothisa (Hull et al., 1991), ephakamisa ukuba i-NAcc DA ayimfuneko ukuze ikopishwe kodwa ikhuthaza ukuqala kwayo.

Ezi zinto zifunyanisiweyo zinokubaluleka kulawulo lwe-serotonergic kwezinye iindlela zokuziphatha. Umsebenzi we-Mesoaccumbens we-DA unegalelo kwimpembelelo yokuqalisa ukusebenza kweendlela ezininzi zokuziphatha ezixhasayo (I-Koob, i-1996; Salamone et al., 1997). Inyani eyonyukayo ye-extracellular 5-HT kwi-LHAA ingathintela i-NAcc ye-DA ukukhutshwa okucebisa ukuba yandise i-LHAA I-5-HT inokuchaphazela iindlela ezininzi zokuziphatha. Umzekelo, i-extracellular DA kwi-NAcc iphakanyisiwe ngaphambi nangexesha lokutya kunye nokuwa emva kwexesha elithile (Wilson et al., 1995). Ngapha koko, ukukhutshwa kwe-LHA 5-HT kunyuka ngexesha lokutya kwaye kuye kwacetyiswa njengenye into ekhuthaza ukugcwala (I-Schwartz et al., 1989; I-Aoyagi et al., 1992). I-DA, kunye ne-5-HT, kwi-LHA inokuthintela ukukhutshwa kwe-NAcc DA kunye nokuqiniswa kokuziphatha (Parada et al., 1995). Ke ngoko, zombini i-5-HT kunye nokukhululwa kwe-DA kwi-LHAA Inokuba yinxalenye yomjikelezo we-neural oxanduva lokuphelisa ukungaziphathi kakuhle, mhlawumbi ngokuthintela ukuvuselelwa kwe-NAcc DA.

Idatha yangoku inokubonelela ngolwazi lweziphumo zomsebenzi otshintshile we-5-HT kumbane wokuzivuselela kwengqondo kunye nokuzilawula kwiziyobisi ngokwakho. Ezi ndlela zokuziphatha ziphantsi kolawulo lwemisebenzi ye -accaccumbens ye-DA (ukuphononongwa kwakhona, yabona Di Chiara, 1995) kwaye inokuphuculwa okanye ukuthintelwa ngokunciphisa okanye ukwanda, ngokulandelanayo, i-5-HT neurotransuction [ukukhuthaza ubuchopho bengqondo (I-Poschel kunye neNinteman, 1971; Katz noCarroll, 1977; I-Montgomery et al., 1991; Abantu abadala kunye ne-Yuwiler, i-1992; UFletcher et al., 1995) kunye nolawulo lobuchwephesha bokuzilawula ngokwamachiza (UCarroll et al., 1990a,b; I-Loh kunye neRoberts, i-1990; I-Richardson kunye neRoberts, i-1991)]. Kukho, nangona kunjalo, ingxelo yakutshanje ebonisa ukuba ukukhuthaza kwe5-HT1BI-receptor subtype inokwenyusa ukuqiniswa kwe-cocaine kwaye ke yindlela yokuziphatha ye-cocaineI-Parsons et al., 1998). Nangona kunjalo, iziphumo zangoku zibonisa indawo ephakathi enokuthi ihambisane neempembelelo zoxinzelelo ze-5-HT kwiindlela zokuzivuselela kunye nokuziphatha. Ke, i-LHAA I-5-HT inokuba yinto ebalulekileyo ekufuneka uyiqwalasele xa kusenziwa amacebo okunyanga ukusetyenziswa gwenxa kweziyobisi.

Ukuqukumbela, i-extracellular DA kwi-NAcc yanda ngexesha lokukhuphela kodwa yancipha emva kwe-ejaculation. Ukuphakamisa i-LHAA I-5-HT nge-reverse dialysis iyancipha kwi-extracellular DA ngexesha zombini iimeko ezisisiseko kunye nokukhuphela. Ezi datha, kunye neziphumo zangaphambili (Lorrain et al., 1997), cebisa ukuba i-LHAA I-5-HT isebenzisa ulawulo lwe-inhibitory ngaphezulu kokukopishwa, ngokuyinxenye, ngokuthintela ukukhutshwa kwe-NAcc DA emva kwe-ejaculation. Olu phando luneziphumo ezibalulekileyo zeklinikhi kwabo bathatha ii-antidepressants ze-SSRI, iziphumo ebezingalindelekanga ezinokuphazamiseka kwendlela yokusebenza ye-ejaculatory kunye ne-orgasmic kunye ne-libido enciphile. Ikwacebisa indawo esembindini apho i-5-HT inokuthi ikhuphe ulawulo lwezinye iindlela zokuziphatha ezishukunyiswayo.

Icandelo langaphambiliIcandelo elilandelayo

Imihlathi

    • I funyenwe Epreli 9, 1999.
    • Zamkelwa Juni 11, 1999.

  • Olu phando luxhaswe liZiko leSizwe leSibonelelo seMpilo yeNgqondo MH40826 kwi-EMH

    Imbalelwano mayibhekiswe kuGqr. Elaine M. Hull, iSebe lezeengqondo, kwiYunivesithi yaseNew York eBuffalo, eBuffalo, kwi-NY 14260.

    Idilesi yakhe ngoku kaGqr.

    Idilesi kaMongameli kaDkt Matuszewich ngoku: iSebe leengqondo, iYunivesithi yaseWestern Reserve, i11100 Euclid Avenue, Cleveland, OH 44106-5000.

Icandelo langaphambili

 

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