Lateral Hypothalamic Serotonin Inhibits Nucleus Accumbens Dopamine: Tlhaloso ea ho Sebetsana le ho Kopanela Liphate (1999)

Journal of Neuroscience, 1 Loetse 1999, 19(17): 7648-7652;


+ Boikarabello ba Mongoli

  1. 1 Lefapha la Psychology, State University of New York ho Buffalo, Buffalo, New York 14260

inahaneloang

Dopamine (DA) e lokolloa libakeng tse 'maloa tsa boko, ho kenyelletsa le li-nucleus accumbens (NAcc), pele le nakong ea ho kopitsoa ho likhoto tsa banna. Bo-ramahlale ba DA ba laetsoeng sebakeng sena ba nolofalletsa, 'me bahanyetsi ba DA ba thibela, boitšoaro bo bongata bo susumetsang, ho kenyelletsa boitšoaro ba banna ba thobalano. Serotonin (5-HT) hangata ha e thibele mekhoa ea monna ea thobalano. Re tlalehetse pejana hore 5-HT e lokolloa sebakeng sa anterior lateral hypothalamic (LHAA) le hore serotonin e khethollang inhibitor e kenngoeng sebakeng seo e liehisitsoe ebile e liehisitsoe ho kopitsoa. Liphetho tsa rona tsa hona joale, li sebelisa li-Micromaalization tsa sebata se phahameng, (1) li netefatsa bopaki bo fetileng ba hore maemo a extracellular a keketseho ea DA ho NAcc nakong ea ho qopitsoa le ho fokotseha nakong ea karohano ea postejaculatory (PEI) le (2) e senola hore LHAA 5-HT e ka thibela thibelo ea DA ea basal le e tšehetsang basali ho NAcc. Liphumano tsena li fana ka maikutlo a hore potoloho ea neural e khothalletsang quiescence ea thobalano nakong ea PEI e kenyeletsa tlhahiso ea serotonergic ho LHAA, eo ka lehlakoreng le leng e thibelang ho lokolloa ha DA ho NAcc. Liphumano tsena li kanna tsa fana ka leseli mabapi le taolo ea boitšoaro bo sa thibeleng ba boitšoaro bo bong bo susumetsoang ke NAcc mme bo ka ba le bohlokoa ba ho utloisisa litla-morao tsa thobalano tse tloaelehileng ho litlhare tsa litlhare tsa litlhare.

Boitšoaro ba botona ba botšehali ho batho, li-primates tse se nang botho le litoeba li susumetsoa ke dopamine (DA) le serotonin (5-HT) neurotransmission (Bitran le Hull, 1987; Gorzalka et al., 1990; Zajecka et al., 1991; Meston le Gorzalka, 1992; Wilson, 1994; Melis le Argiolas, 1995). Ka kakaretso, DA ea ntlafatsa, athe 5-HT e thibela, ts'usumetso ea thobalano le ts'ebetso mme ka hona e ka kenya letsoho ho qalisong le ho satiety, ka ho latellana.

Boteng ba tšusumetso e amanang le thobalano, DA ea kantle ho naha e eketseha ka har'a li-nucleus accumbens (NAcc) (Mas et al., 1990; Pfaus et al., 1990; Damsma et al., 1992; Fiorino et al., 1997) le sebaka sa medial preoptic (MPOA) (Hull et al., 1995) ea likhoto tsa banna; Maemo a DA a eketseha le ho feta nakong ea ho kopitsoa. DA e lula e phahame ho fihlela e thunya e tona, ka mor'a moo maemo a DA a fokotseha (Blackburn et al., 1992). Kamora nako ea ho khaotsa ho ts'oaroa ka thobalano (PEI) ya ho nyatsa thobalano, ho qopitsa ho qala hape mme ho bapisoa le tokollo e ntlafalitsoeng ea DA. Mokhoa ona o thusitse ho hlalosa karolo ho DA ho tataiseng boitšoaro ba banna ba thobalano. Leha ho le joalo, lintlha tse thibelang ho lokolloa ha DA kamora ho emisoa (mme ka hona li ka tlatsetsa ho PEI) li fumane tlhokomelo e nyane.

Serotonin ka kakaretso e thibela ho kopitsoa. Boitšoaro ba thobalano bo sithabetsoa ke li-agonists le li-agonist tsa 5-HT tse ngata tse eketsang ho fumaneha ha 5-HT mme e tsamaisoa ke lesapo la serotonergic le bahanyetsi ba bangata ba receptor (Bitran le Hull, 1987; Gorzalka et al., 1990; Wilson, 1994). Liteko tsena li hlohlelletsa mohopolo oa hore XoUMX-HT ea morao-rao e ka lokolloa ka tšohanyetso mme e ka laola PEI. Ex vivo maemo a lithane tsa preoptic tsa 5-HT (Mas et al., 1987) le Ka vivomehato ea preoptic micodialysate ea 5-hydroxyindoleacetic acid [metabolite e ka sehloohong ea 5-HT (Fumero et al., 1994)] e eketsehile haholo feela kamora ho nyaloa. Ka hona, 5-HT e kanna ea lokolloa masimong a seterateng sa serotonergic, ho kenyelletsa le sebaka sa pele, mme e khothaletse ho nyatsa ho kopanela liphate nakong ea PEI. Re sa tsoa lekanya extracellular 5-HT ho MPOA empa ha rea ​​fumana liphetoho nakong ea ho qopitsa kapa kamora ho emisoa (Lorrain et al., 1997). Extracellular 5-HT, leha ho le joalo, e ile ea eketseha sebakeng se haufi sa anterior lateral hypothalamic (LHAA) hang kamora ho khahla. 5-HT ho LHAA ka morao ho moo ea fokotseha ho ba haufi le maemo a mantlha pele motheo o kopitsoa hape. Ntle le moo, microinjection e khethang serotonin reuptake inhibitor (SSRI) ho LHAA ea lietsisa ho qalella ha boqapi (ka mokhoa o ts'oanang le PEI) ea liehisa ho emisoa kamora hore monna a qale ho sebetsa hape (Lorrain et al., 1997). Ka ho hlakileng, 5-HT e lokolloa ho LHAA e inhibitory ho kopitsa mme e ka kenya letsoho ho PEI.

Merero ea 5-HT e qalang raphetong e ka hatella lits'ebetso tsa "catecholaminergic system" tsa "forebrain"Yamamoto le Ueki, 1978). LHAA e fumana tlhahiso ea 5-HT ho tsoa ho raphe (Veening et al., 1982; Vertes, 1991) hape e kenya likhoele tse sebetsang hantle tse nyolohang kapa tse theohang ka bongata ba methapo ea methapo (Saper et al., 1979;Hakan et al., 1992). Re ile ra leka hore na 5-HT e lokollotsoe LHAA e ka hatella ts'ebetso ea thobalano ka ho thibela mokhoa oa DA oa tsebaccumbens. Ha re leka 1 re sebelisitse microdialysis ho netefatsa datha ea electrochemical e fetileng e bonts'itseng tokiso ea NAcc DA nakong ea ho kopitsa le ho fokotsa tokollo kamora ho emisoa. Ha re leka 2, re file 5-HT ho LHAAka diversal e reverse hape ka nako e le ngoe e lekantseng litlamorao tsa eona ho lokolloe ha basali ba NAcc le ba basali ba DA.

LISEBELISOA LE MEKHOA

Lintho. Liroto tsa banna ba leshome le metso e robong ba neng ba phela ka thobalano li ne li bolokiloe ka kotloloho mekotleng ea polasetiki ebe li bolokiloe mochining o khutlang o bobebe / o lefifi ka mabone ho 11: 00 AM le ho 10: 00 PM Lijo le metsi li ne li le teng ad libitum. Bakeng sa liteko tsa 1, lithuto tsa 7 li amohetse cannula ea tataiso e le 'ngoe e etselitsoeng tikoloho ea likhetla ea NAcc [anteroposterior, + 3.0; Mediolateral, + 1.0; le dorsoventral, −5.2 (Pellegrino et al., 1979)]; lithuto tsa 12 tse setseng, tse sebelisitsoeng teko ea 2, ka ho eketsehileng li ile tsa amohela ipsilateral tataiso cannula e ikemiselitseng ho LHAA[anteroposterior, + 1.3; Mediolateral, + 1.5; le dorsoventral, −7.2 (Pellegrino et al., 1979)]. Kamora nako ea beke ea 1 ea ho hlaphoheloa, ho ile ha qala libaktheria tsa maiketsetso. Ts'ebetso tsohle li ile tsa latela tataiso ea mme tsa amoheloa ke Komiti ea Tlhokomelo ea Liphoofolo le Ts'ebeliso ea lehae.

Microdialysis. Concentric micodialysis probes e entsoe ka lab. Ka bokhutšoaane feela, 27 ga-wall e se nang tšepe ea tšepe e ne e entsoe ka lesapo la mokokotlo [12,000 kDa cutoff; 210 μm bophara ba kantle (od); 1 mm e sebetsang-dialyzing holim'a lefatše; Spectra Por, Houston, TX] pheletsong e le 'ngoe ea 3 cm ea polyethylene 20 tubing pheletsong e' ngoe ho sebeletsa e le setsi sa polokelo ea bohareng. Sekhechana sa 20 cm ea silica capillary tubing [125 μm od; 50 μm bophara ba ka hare (id); Polymicro Technologies, Phoenix, AZ], e kenelletse ka mokokotlong oa dialysis, e sebelisoa e le setsi. Bakeng sa liteko tsa 1, sekhahla sa phallo ea dialysate e ne e le 1 μl / min; disampole li ne li bokelloa metsotso e meng le e meng ea 3 ka meqomong ea microcentrifuge (250 μl), e behiloe leqhoeng le omileng, 'me e kenngoa kahare ho 1 hr kh'orong ea capillary bakeng sa ho sekaseka mahloriso a DA ke HPLC ka tlhahlobo ea electrochemical (HPLC-EC). Bakeng sa liteko tsa 2, sekhahla sa phallo ea dialysate e ne e le 0.5 μl / min, 'me mehlala e ne e bokelloa metsotso e meng le e meng ea 10. Bakeng sa liteko tse ka bobeli, dialysis perfusion medium e ne e le tharollo ea Ringer e ntlafalitsoeng e neng e entsoe ka 138 mm NaCl, 2.7 mm KCl, le 1.2 mm CaCl2, pH 7.0. Potoloho e ne e laoloa ke pompo ea infringe ea Harvard syringe (mohlala 22; Cambridge, MA). Hoseng ka karolo e 'ngoe le e' ngoe ea microsalysis, lithuto li ne li sa kenngoe hanyane ka ether ho lumella ho kenngoa ha lipatlisiso tsa microsalysis. Ho phalla ha dialysate ho qalile hanghang, mme nako ea ho tsitsisa ea 5 hr e ile ea lumelloa pele pokello ea sampole e qala. Lintlha tsohle tsa Microbalalysis li hlahisoa e le liperesente tsa motheo [o thehiloe ka ho nka karolelano ea li-sampuli tse tharo tse latellanang tsa tlhahlobo (liteko tsa 1) kapa li-preroc (liteko tsa 2).

HPLC. Ho sibolloa ha DA ho phethetsoe ho sebelisa capillary HPLC-EC. Mohlala o mong le o mong o ne o kenngoa ka letsoho ho kenya valveor ea enjene ea VALCO, e isang 500 nl kh'olong ea capX ea C18 reverse-phase capillary (0.3 mm id × 5.0 cm; 3 μm sp ;res; LC Packings, San Francisco, CA). Mohato oa mobile o ne o le 30 mm citric acid, 50 mm sodium acetate, 0.027 mmNa2EDTA, le 0.25 mm octyl sodium sulfate, e nang le 2.5% acetonitrile le 0.2% tetrahydrofuran (v / v), pH 3.6, mme e hlahisitsoe e sebelisa mofuta oa Gilson, Inc. (Middleton, WI) 307 pompo e sebetsang ho 0.5 ml / min ebile e na le phallo ea Acurate. splitter (LC Packings). Sekhechana sa phallo se fane ka 6 /l / min ea sebaka se se nang sekoli sa pulsation ho ea khokahanong ea tlhahlobo. Dopamine oxidation e fumanoe ka molaoli oa laolo la Antec DECADE (Leiden, Netherlands) a sebelisa selefouno e tsamaeang ka bongata (molumo oa 11 nl) e nang le "electrode" ea khalase e sebetsang e hlahisitsoeng ka mokhoa o ka khonehang oa X 0.7 V e amanang le electrode ea Ag / AgCl. Sistimi ena e ne e lekantsoe letsatsi le letsatsi ka tekanyetso ea DA e sa tsoa lokisoa kopanong ea 1 pg / μl (0.5 pg khorong).

Mekhoa ea tsamaiso. Ha a ntse a leka 1, kamora nako ea ho tsitsa ea 5 hr le kamora ho bokella sampole ea dialysate ea baseline, mosali e moholo oa semmuso o ile a hlahisoa lebaleng la liteko la monna, mme ho qopitsa ho qalile. E tona e ne e lumeletsoe ho kopitsa lintho tse ka bang tharo. Ka nako ena, mehlala e ne e bokelloa ka har'a libini tsa 3 min ebe e ngotsoe e le e bokelloang nakong ea ho qopitsoa (COP) le e ileng ea bokelloa nakong ea thobalano ka mora thipa. Lihlopha tse tharo tsa sampuli (tse ipapisitseng le boitšoaro ba monna nakong ea ho bokella) li ile tsa thehoa bakeng sa tlhahlobo ea HPLC ea morao-rao ea litaba tsa DA: basement (BL), COP, le PEI.

Ho leka 2, kamora nako ea ho tsitsa ea 5 hr le kamora ho bokelloa ha sampole ea motheo ka projeke ea microsalysis e fumanehang ho NAcc, phallo e qaliloe proheneng e fumanehang ho ipsilateral LHAA, e tsamaisitseng 5-HT [1 mg / ml (5.6 m. mm); Sigma, St. Louis, MO] kapa koloi (tharollo ea Ringer). Li-sampuli tsa diialysate li ntse li tsoela pele ho bokelloa ho tsoa ho NAcc ka li-bins tsa 10 min nakong ea 40 min ea LHAA tlotsa. Ho etsa tlhahlobo ea 5-HT khatello ea tokollo e entsoeng ka tšohanyetso ea NAcc DA, re ile ra beha mosali ea emeng lebaleng la liteko la monna nakong ea ho bokella sampole ea ho qetela, ka nako e le ngoe le LHAA Phodiso ea 5-HT (ke hore, nako, metsotso ea 30-40 kamora 'basel). Ba batona bohle ba bontšitse boitšoaro bo bong ba thobalano; leha ho le joalo, ts'ebetso ea bona ha ea ka ea fosoa.

Bohlale. Kamora seboka sa Microbalalysis, liphoofolo li ile tsa khahloa ka ho teba ka sodium pentobarbital, 'me dae ea cresyl violet e ile ea ntlafatsoa ka ho bona (li-probe) tsa microsalysis. Likarolo li ile tsa hlakoloa, 'me meea ea tsona ea tlosoa hore e netefatsoe ka nalane ea liphuputso. Ke liphoofolo feela tse nang le dae e putsoa sebakeng sa NAcc (liteko tsa 1) le LHAA(liteko tsa 2) li sebelisitsoe bakeng sa tlhahlobo ea lipalo.

Tlhahlobo ea lintlha. Bakeng sa liteko 1, joalo ka ha ho boletsoe kaholimo, dialysate e bokelletsoeng ho tsoa ho NAcc e arotsoe ka mekhahlelo e meraro ea boitšoaro: BL, COP, le PEI (e hlahisitsoeng joalo ka liperesente). ANOVA e le 'ngoe e ile ea etsoa ka liperesente tse kholo tsa DA bakeng sa lihlopha tsena tse tharo. Hobane liteko tsa maemo li ile tsa hloleha (p <0.001), ANOVA ea Kruskal-Wallis e ile ea etsoa ka tatellano, ea lateloa kepost hoc bapisa ho sebelisa mokhoa oa Dunn. Bakeng sa liteko tsa 2, ho ile ha sebelisoa mekhoa e 'meli e pheta-phetoang ANOVA, e nang le mafura (5-HT vs koloi) e le eona pakeng tsa factor le nako (6 kapa 10 min dialysis bins) e le eona ntho e ka hare, ho leka litlamorao tsa 5-HT ho kenella ka har'a LHAA maemong a NAcc DA.Post hoc Papiso ea Scheffé e entsoe ho latelaKirk (1968).

LIPOTSO

Teko 1: Ho lokolloa ha DA ho NAcc nakong ea ho qopitsa le kamora ho emisoa

Ho lokolloa ha DA ho NAcc ho latela mohlala o bonts'itsoeng oa karolo ea ts'ebetso bakeng sa neurotransmitter ena ho e kopitsa. Sebopeho se tloaelehileng sa phoofolo e le 'ngoe se ka bonoa ho Setšoantšo1 A; Ho lokolloa ha DA ho ne ho phahame nakong ea ho kopitsoa empa ho fokotsehile kamora ho omisoa ka seng (ke hore, nakong ea PEI). ANOVA e maemong a ya data e hlophisitsoeng e senotse phapang ea bohlokoa mefuteng ea li-daalysate ea DA maemong ohle a boitšoaro [H(2) = 14.794; p <0.001; Setšoantšo 1 B]. Post hoc lipapiso li bonts'itse hore DA e ne e phahame haholo ka har'a mehlala e bokelitsoeng nakong ea ho qopitsoa, ​​ha e bapisoa le e bokelitsoeng nakong ea BL kapa PEI (p <0.05).

Setšoantšo sa 1.

Ka vivo microdialysis ea DA e lokolloe ho NAcc ea likhoto tsa banna nakong ea lithuto tsa thobalano.A, Mohlala oa baemeli ba liphetoho tsa nakoana tempeleng e le 'ngoe. B, Ho bolela phetoho tokollong ea DA (± SEM) bakeng sa sehlopha sa likhoto tse tšeletseng. Mehlala e ile ea bokelloa ka makhetlo a 3 min nakong ea mekhahlelo e meraro ea kemiso ea mmele 'me e khethiloe e le blopulatory BL (mekoloko e tletse), COP (bulehileng mekotla), kapa PEI (likhoele tse hlekiloeng). Litaba tsa Dopamine li ne li le ngata haholo ka har'a disampole tse bokelitsoeng nakong ea ho kopitsoa, ​​ha li bapisoa le disampole tse bokelitsoeng tlasa maemo a BL le a PeI (**p <0.05).

Teko ea 2: litlamorao tsa 5-HT ho LHAA ho DA ho NAcc

Revers dialysis ea 5-HT e kene ho LHAAe fokolitse tokollo ea basal ea NAcc DA mme e boetse e thibela tokollo e ntlafalitsoeng e bonoang ka tloaelo nakong ea ho kopitsoa.2). ANOVA e entsoeng mabapi le lintlha tsena e bone phello e kholo ea lihlopha [F (1,10) = 46.324; p<0.001] le nako [F (5,50) = 11.232; p <0.001] le tšebelisano ea sehlopha xF (5,50) = 22.876;p <0.001]. Post hoc papiso e senotse hore DA e ne e le tlase haholo ho sampuli e 'ngoe le e' ngoe ea dialysate tse bokellelitsoeng nakong ea 5-HT perfusion, ha e bapisoa le boleng ba motheo (p <0.05). Liphoofolo tse amohelang koloi ho LHAA e bontšitse keketseho e kholo ho moaheli oa NAcc DA ho ea ka motheo (p <0.05) nakong ea tšebetso; leha ho le joalo, ha ho keketseho e joalo e bonoeng liphoofolong tse amohelang 5-HT ho LHAA.

Setšoantšo sa 2.

Phetoho ea nakoana litlamong tsa DA tsa dialysate tse bokelletsoeng ho tsoa ho NAcc pele le nakong ea 40 min ea 5-HT perfusion ho LHAA ea likhoto tse tšeletseng tsa banna. Mehlala e ile ea bokelloa ka linako tsa 10 min. Ho ile ha tsebisoa mosali e motšehali, 'me ho kopitsoa ho ile ha lumelloa nakong ea ho bokelloa ha sampole ea hoqetela nakong ea ha 5-HT e tlatsitsoe. Ho fokotseha ho hoholo ho DA ho etsahetse ho pholletsa le nako eohle ea 5-HT ea ho etsoa. Phekolo ena e thibetse keketseho ea tokollo ea NAcc DA e bonoang ho liphoofolo tse laoloang [*p <0.05, linako tsa pherekano vs nako ea 0 (motheo)]. VEH, Koloi.

TŠOHLOA

Liphumano tsena li bonts'a khokahano ea methapo pakeng tsa methapo ea methapo ea kutlo le mesolimbic ea boko e ka holisang quyscence ea thobalano nakong ea PEI. Ka liteko 1 re thehile hore maemo a DA a kantle ho karolelano ea keketseho ea NAcc ea likhoto tsa banna nakong ea ho kopitsa empa e ea fokotseha kamora ho emisoa, nakong ea PEI. Liphetho tse tšoanang li tlalehiloe, li thehiloe ho Ka vivomahlale a chronoamperometric (Phillips le al., 1991). Leha mekhoa e joalo e na le tharollo e kholo ea nakoana, e ke ke ea hlakola litefiso tsa DOPAC le acid e phahameng haholo ho tloha ho DA ho ea lets'oaoong (Dayton et al., 1981; Gonon et al., 1984). Haufinyane, sebelisa Ka vivo Microbialysis, e nang le pheko e ntle ea methapo, Fiorino et al. (1997) etsa qeto ea hore ho ba le maikutlo a botona kapa botšehali ho amana le ho se khonehe ha mosali ea ts'oanelang ho etsa hore ho be le keketseho ea maemong a NAcc DA. Thutong eo ho sebelisitsoe nako ea sampole ea 15 min, ho thibela tlhaloso ea tatelano ea motho ka mong. Teko ea hona joale e sebelisitse nako ea sampling ea 3, ho fana ka lekhetlo la pele ka bobeli qeto e phahameng ea nakoana le tharollo ea methapo ea maikutlo tlhahlobisong e ntle ea tokollo ea DA nakong ea liketsahalo tse ikhethang. Matlafatso ea tokollo ea NAcc DA nakong ea ho kopitsa e ne e sa bolokoa ho pholletsa le PEI. Sena se fana ka maikutlo a hore thepa e matlafatsang ea DA ea mosali oa botšehali e tlhotliloe ka tsela e itseng kapa e thibeloa hang hang ka mor'a ho emisoa.

Maemo a hamorao a hypothalamic 5-HT, a eketsehang kamora ho emisoa, a ka kenya letsoho ho quiescence ea thobalano ea PEI. Ho tsamaisa 5-HT ho LHAA ka diversal e reverse tekong ea 2, joalo ka kemolo, e hlahisitse phokotseho ea hanghang ea litekanyetso tsa extracellular tsa DA ho NAcc. Dopamine e ile ea tsoela pele ho fokotseha butle ka nako eohle ea tsamaiso ea 5-HT. Phekolo ena e boetse e thibetse keketseho ea DA ea basali ba phahameng eo hangata e amanang le ho kopitsa.

Re tlalehetse haufinyane hore extracellular 5-HT e eketsehile ho LHAA kamora ho emisoa; microinjection ea SSRI sebakeng sena e liehisitse ho qala hoa thobalano (ka mokhoa o ts'oanang le PEI) mme ea liehisa ho phahama ha semolao ka mora ho qopitsoa empa ha ea ka ea kena-kenana le taba-kakaretsoLorrain et al., 1997). Lintlha tsena, hammoho le liphumano tsa morao-rao, li fana ka maikutlo a hore ho emisa ka tšohanyetso kamora ho fetoloa hoa kemolo ho ka ba, ka karolo e laoloang ke tokollo ea 5-HT ho LHAA le thibelo e hlahlamang ea mesoaccumbens DA. Tlas'a maemo a tloaelehileng, DA e lokolloa kahare ho NAcc ea likhoto tsa banna ha lits'oaetso tsa estrous li le teng (Louilot et al., 1991; Damsma et al., 1992). DA ena e kanna ea etsa hore e tona e kopane le mosali. Liphofu tse fokotsang tsa DA tsa NAcc li theotse palo ea manonyeletso a karabelo ha a araba maikutlong a hole a tsoang ho mosali ea motšehali mme a liehisa ho qalella ho kopitsoa (Liu et al., 1998). Nakong ea PEI, NAcc DA e fokotseha (liteko tsa 1), joalo ka ha ho bonahala tsoelo-pele ea thobalano ho mosali. Ho eketseha ha 5-HT ho LHAA e kanna ea ba ntho ea bohlokoa e sitisang ts'ebetso ea li-neuronal eo ka tloaelo e qobellang mesoaccumbens DA le boits'oaro bo bobebe.

Taolo ea thibelo ea ts'oaetso nakong ea thobalano ke karolo ea bohlokoa ea katleho ea botona. Ha ho qalella ho kopitsa ho sa le morao ho ka hlakola semela se tlotsitsoeng se emelang pele ho fetela ka popelong ea mosali (Adler le Zoloth, 1970; Sachs, 1982); Ho feta moo, ejaculate ea bobeli e hlahang kapele kamora hore ea pele e be le peoana e nyane ho feta e fetileng. Quiescence ea thobalano ea PEI ha se lebaka la ho se atlehe ha erectile; Mekhabiso e hlakileng e bolokoa, kapa e hlile ea ntlafatsoa, ​​ke kemiso e fetileng (O'Hanlon le Sachs, 1980). Ka hona, ho bohlokoa hore e tona (le mosali) e thibeloe ka tšusumetso nakong ea PEI ho khothaletsa bokhachane bo atlehileng. Ho fokotseha ka nako e tšoanang ho LHAA 5-HT (Lorrain et al., 1997) le keketseho ea NAcc DA qetellong ea PEI e fana ka tlhahiso ea mokhoa oa ho etsa nako ena ea quiescence ea thobalano. Ho shebeloa ha lits'ebetso tse peli tse kopaneng ha ho hlahise tataiso ea ho hlasimoloha. Leha ho le joalo, ho fumanwa ho arolang mefuta ea 5-HT ho LHAA e fokotseha maemo a tsoang ho DA ho NAcc e fana ka maikutlo a hore ho nyoloha ha XeUMX-HT ho LHAA hangata e baka ho fokotseha ha NAcc DA.

LHAA e kanna ea tšoaneleha hantle bakeng sa ho fetola tlhaiso-leseling e amanang le thobalano ho tsoa ho hypothalamus ho ea bokong bo bong. Karolo ea morao ea hypothalamus e hlalositsoe e le mokhoa o laolang boitšoaro bo botle le bo susumetsang (Benarroch, 1993). Li-neurons tse ngata tsa "lateral hypothalamus" (LH) li ile tsa fetola maemo a bona a ho thunya ka potlako ho latela lijene tsa testosterone kapa estrogen (Orsini, 1982) le ho tsamaisa ts'ebeliso ea lihormone tsena (Orsini, 1985). Ntle le moo, tlhahlobo ea 2-deoxyglucose e hlophisitsoeng hantle ea ts'ebetso ea neural e senotse keketseho ea ts'ebetso ea neural ho LH ho arabela ka monko oa basali (Orsini et al., 1985). Ka hona, li-neuron tsa LH li ka khothaletsa takatso ea monna ea thobalano le / kapa ketso. Ntle le moo, likhahla tsa parasagittal li arola MPOA le LHAA/ medial forebrain khoele ea khoheli khoheli a litoeba tsa banna (Szechtman et al., 1978; Brackett le Edward, 1984).

Bonyane ho na le mekhoa e 'meli e ka sebelisang LHAA Tšusumetso ea 5-HT ka tokollo ea NAcc DA (sa feiga.3). LHA e kenyellelitsoe sehlopheng sa meralo e amanang le sebaka se ka tlasa lefatše, se bontšitsoeng se na le khokahano ea boiphetetso le NAcc (Hakan et al., 1992; Wu et al., 1996). Ho boetse ho na le bopaki ba sebopeho sa tsela e theohang ho tloha LH ho ea sebakeng sa ventral tegmental (VTA) (Wolf le Sutin, 1966; Saper et al., 1979). Ka hona, ho lokolloa ha DA ho NAcc ho ka susumetsoa ka kotloloho ka tsela e nyoloha ho tloha LHA ho ea NAcc kapa ho hlophisoa ka tsela e sa tobang ka tsela e theohelang ho tloha LHA ho ea VTA.

Setšoantšo sa 3.

Seemeli sa merero ea li-circuits tse ka bang teng tsa neural tse amehang ho LHAA 5-HT thibelo ea NAcc DA e lokolloe. Ho lokolloa ha DA ho kanna ha susumetsoa ke 5-HT e sebetsang ho likhakanyo tse tobileng tse tsoang ho LHAA ho NAcc (A) kapa li-neurons tse sa lebelloang tse sa fihlelleng ho VTA (B). E fetotsoe ho tsoa Paxinos le Watson (1982). MFB, setlama sa litlokotsebe sa mori.

Sebaka sa terminal sa NAcc se na le likarolo tse peli tse kholo tsa mantlha, khetla le konokono (bakeng sa tlhahlobo, bona Deutch et al., 1993). Phuputsong ea hona joale, lipehelo tsa tlhahlobo ea microsalysis li ne li behiloe feela khetla ka hona li bonts'a LHAA Taolo ea 5-HT e tsamaisang subregion ena. Ha ho hlake hore na mantlha e na le tšusumetso e tšoanang. Tlhahisoleseling e joalo e ka fana ka leseli mabapi le phapang lipakeng tsa likarolo tsena tse peli taolong ea boits'oaro bo susumetsang.

Leha kopollo e sa ka ea hlahisa karabelo ea DA ho NAcc ipsilateral ho 5-HT reverse dialysis (liteko 2), banna bohle ba ile ba khona ho etsisa, mohlomong ka lebaka la ketso e tloaelehileng ea DA maemong a sa sebetseng a kontraka ea selekane. Meetso ea Boitšoaro e ne e sa tlaleheloa, ka hona ha ho khonehe ho tseba hore na liphoofolo tsa 5-HT li ne li fapane le taolo. Le ha ho le joalo, li-microinjection tse peli tsa SSRI li kena LHAA O ile oa lieha, 'me a qopitsa butle ho etsa liteko tse fetileng (Lorrain et al., 1997). Liphoso tse felisang khatello tsa DA tsa NAcc le tsona li liehisitse ho qalella ha ho qopitsoa (Liu et al., 1998), le ho fokotsa tokollo ea NAcc DA e lietsitseng le ho lieha ho kopitsoa (Hull et al., 1991), ho fana ka maikutlo a hore NAcc DA ha e hlokehe bakeng sa ho kopitsoa empa e khothaletsa ho qala ha eona.

Liphumano tsena li ka ba le bohlokoa ba taolo ea serotonergic holim'a boitšoaro bo bong. Ts'ebetso ea Mesoaccumbens DA e etsa hore ho be le tšusumetso ea ts'ebetso ea mefuta e mengata ea boits'oaro bo susumetsoang (Koob, 1996; Salamone et al., 1997). Taba ea hore e eketsehile extracellular 5-HT ho LHAA e ka thibela NAcc DA tokollo e fana ka maikutlo a hore eketseha LHAA 5-HT e ka ama boits'oaro bo bongata. Mohlala, DA ea kantle ho naha ho NAcc e phahamisoa pele ho nako ea lijo mme e oela nakoana kamora moo (Wilson et al., 1995). Ho feta moo, tokollo ea LHA 5-HT e eketseha nakong ea ts'ebeliso ea lijo mme ho fanoe ka tlhahiso e le ntlha e le 'ngoe e khothalletsang satiety (Schwartz et al., 1989; Aoyagi et al., 1992). DA, hammoho le 5-HT, ho LHA ​​e kanna ea thibela NAcc DA ho lokolla le ho matlafatsa boitšoaro (Parada et al., 1995). Ka hona, 5-HT le DA li lokollotsoe ho LHAA e ka ba karolo ea "neural circry e ikarabellang ho feliseng boits'oaro ba takatso ea lijo, mohlomong ka ho thibela ts'ebetso ea NAcc DA e susumetsoang.

Lintlha tse teng hona joale li kanna tsa fana ka leseli mabapi le litlamorao tsa mosebetsi o fetotsoeng oa 5-HT mabapi le ho itlhasimolla bokong le ho itaola kahare ho lithethefatsi. Boitšoaro bona bo tlas'a taolo ea tšebetso ea DA eaaccaccumbens (bakeng sa tlhahlobo, bona Di Chiara, 1995) mme e ka ntlafatsoa kapa ea thibeloa ka ho fokotseha kapa ho hola, ka ho latellana, 5-HT neurotransmission [tšusumetso ea kelello ea motlakase (Poschel le Ninteman, 1971; Katz le Carroll, 1977; Montgomery et al., 1991; Bacha le Yuwiler, 1992; Fletcher et al., 1995) le taolo e kenelle ea lithethefatsi (Carroll et al., 1990a,b; Loh le Roberts, 1990; Richardson le Roberts, 1991)]. Ho na le leha ho le joalo, ho na le tlaleho ea morao-rao e bonts'ang khothatso ea 5-HT1Breceptor subtype e kanna ea ntlafatsa ntlafatso ea koae 'me ka tsela eo, boitšoaro ba ho itlhokisa (cocaine)Parsons et al., 1998). Le ha ho le joalo, liphetho tsa hona joale li fana ka maikutlo a sebaka sa mantlha se ka arolelanang litlamorao tsa 5-HT ka boits'oaro ba boits'oaro le boithuto. Kahoo, LHAA 5-HT e kanna ea ba ntlha ea bohlokoa e lokelang ho nahanoa ha ho etsoa maano a phekolo ea tlhekefetso ea lithethefatsi.

Qetellong, DA ea kantle ho naha ho NAcc e eketsehile nakong ea ho kopitsoa empa ea fokotseha kamora ho emoloa. Ho phahamisa LHAA 5-HT ka reverse dialysis e fokotsehile extracellular DA nakong ea maemo le litheko tse tlase. Lintlha tsena, hammoho le liphumano tse fetileng (Lorrain et al., 1997), fana ka maikutlo a hore LHAA 5-HT e fana ka taolo ea thibelo lipapisong, ka karolo e itseng, ka ho thibela NAcc DA tokollo kamora ho emisoa. Patlisiso ena e na le litlamorao tsa bohlokoa tleleniking ho ba nkang li-antidepressants tsa SSRI, litlamorao tse kholo tsa eona e le ho sitisoa ke bokhoni ba ho feto-fetoha ha matla le boits'oaro le ho fokotsa libido. E boetse e fana ka maikutlo a sebaka sa mantlha seo ho sona 5-HT e ka fanang ka taolo ea boits'oaro ka mekhoa e meng e susumetsoang.

Mongolo o botlaaseng ba leqephe

    • E amohetse April 9, 1999.
    • E amohetse June 11, 1999.
  • Patlisiso ena e tšehelitsoe ke National Institute of Mental Health Grant MH40826 ho EMH

    Litaba li lokela ho lebisoa ho Dr. Elaine M. Hull, Lefapha la Psychology, State University of New York ho Buffalo, Buffalo, NY 14260.

    Aterese ea hona joale ea Dr. Lorrain: Lefapha la Psychiatry, Univesithi ea Chicago, MC 3077, 5841 South Maryland Avenue, Chicago, IL 60637.

    Aterese ea hona joale ea Dr. Matuszewich: Lefapha la Psychiatry, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5000.

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