Liphetoho Tse Matla Nucleus Accumbens Dopamine Efflux Nakong ea Coolidge Methati ea Male Rats (1997)

LIPOTSO

Neurochemistry

Basal nanomolar ho tsepamisa maikutlo ho DA le metabolites ea eona ka har'a micodealysates, e hlahisitsoeng e le moelelo ± SEM, ea mehlala ea pele e meraro ea motheo e ne e le: DA, 3.0 ± 0.7; DOPAC, 619.1 ± 77.7; le HVA, 234.2 ± 49.0 (ha e ea nepahala bakeng sa ho hlaphoheloa ha probe;n = 5). Lits'ebetso tsena li emetse lintlha tsa motheo tsa 100%.

Lintlha tsa tlhaiso-leseling tse hlalositsoeng ka boitsoaro, tse tsamaellanang le karolo ka 'ngoe ea liteko le tse tloaelehileng ho rat e' ngoe le e 'ngoe, li ile tsa sebelisoa bakeng sa tlhahlobo ea methapo ea kutlo. Tsena li kenyelelitse tse latelang: (1) disampole tse supileng kamora ho kenyelletsoa ha 1 ea mosali oa pele, (2) disampole tse 'ne tse tsamaeang le ho se be teng ha boitšoaro bo kopanetsoeng le mosali 1, le (3) disampuli tse hlano kamora tlhahiso ea 2 ea basali. Setšoantšo 1 e bonts'a liphetoho lipakeng tsa DA (graph graph, Bohareng) le li-metabolites tsa DA (graph graph tlhōrōng) tsela e tšoanang ea ho kopana (setšoantšo sa bar, Tlase) nakong ea liteko bakeng sa phello ea Coolidge.

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Setšoantšo sa 1.

Li-nyuklea li bokellana ka nepo ea methapo ea boitšoaro ba thobalano nakong ea phello ea Coolidge. Mehlala e robeli ea pele e emela lintlha tsa data tse tsoelang pele ho latela nako ho tloha lipakeng tsa 1 ho 3. Mohlala 1 ke mohlala oa bone le oa ho qetela oa ho beleha (Bas). Mohlala 2 e emetse tlhahiso ea 1 ea basali ka morao ho skrini (Moq). Kamora metsotso ea 15, skrine e ile ea tlosoa, 'me likhoto tsa lumelloa ho etsisa (sampuli 3-8). Thekhefu ka x-axis e tsamaellana le ho kenyelletsoa ha data ho likhoto tse tharo tse ileng tsa sebetsa nako e telele le mosali oa pele. Mehlala e robong ea ho qetela e ne e boetse e le tatellano ea liketsahalo ho ea ka nako ea tsona. Mehlala 9 le 10 li lumellana le nako ea satiation ea phase 3 (ke hore, 30 min ntle le thaba). Female 1 e ile ea khutlisetsoa ka morao ho skrineng (sampole 11) mme, 15 min hamorao, skrini e ile ea tlosoa (mohlala 12). Kamora metsotso e 15 e se na ho qopitsoa, ​​2 ea basali e ile ea beoa kamora skrini (mohlala 13). Mehlala 14-17 e tsamaisana le ho qopitsoa le 2 ea basali. Palo ea litefiso, manonyeletso, kapa li-ejaculations tse amanang le sampuli e ngoe le e 'ngoe ea 15 min e bontšitsoe ho tlase bar graph. Lintlha tsa Neurochemical li hlahisoa ho latela liperesente tsa likhakanyo tsa motheo. Liphetoho ho NAC DA (mabala a koetsoeng), DOPAC (mekotla e koetsoeng), le HVA (bulehileng mekotla) efflux e hlahisoa joalo ka li-graph graph. Papiso e latelang e entsoe: sampole ea 1 ea mantlha le li-sampuli 2-10; sampole e ncha ea mantlha ea 10 ha e bapisoa le mehlala ea 11 le 12; sampole e ncha ea mantlha ea 12 ha e bapisoa le mehlala ea 13-17 (*p <0.05; ** p <0.01). Ikemetseng t Liteko li entsoe lipakeng tsa boleng ba motheo (sampole 1, 10, le 12). Bakeng sa liphapang tse kholo ho tsoa ho motheo oa pele (mohlala 1), †p <0.05.

Li-ANOVA tse arohaneng tsa tsela e le 'ngoe, tse entsoeng khafetsa li ile tsa etsoa ho data ea neurochemical e amanang le 1 ea basali (sampuli 1-12) le 2 ea basali (sampuli 12-17). A priori papiso e entsoe ka ho sebelisa liteko tse ngata tsa papiso tsa Dunn (Bonferroni t). Papiso ea mantlha e meraro e latelang e entsoe: (1) basement ea mantlha (sampole 1) khahlanong le sampole 2-10 (tlhahiso ea pele ea 1 ea basali), (2) basement ea bobeli (sampole ea 10) khahlanong le disampole tsa 11 le 12 (ho bontšoa bocha ha 1) , le (3) motheo oa boraro (sampole 12) khahlanong le sampole 13-17 (tlhahiso ea mosali 2).

Ho bile le phetoho e kholo ea kakaretso tsamaisong ea DA ho araba 1 ea basali [F_(11,44) = 8.48; p <0.001] le basali ba 2 [F_(5,20) = 2.83;p <0.05]. Keketseho e kholo ea mokelikeli oa DA e fumanoe ha mosali oa 1 a le teng kamora skrineng (+ 44%,p <0.05; sampole 2). Nakong ea ts'ebetso, lipalo tsa DA li ile tsa eketseha ho ea pele, tsa fihla boleng bo holimo (+ 95%;p <0.01) nakong ea bout ea pele ea copulatory (sampole 3). DA e ile ea lula e phahame nakong eohle ea ho kopitsa 'me ea khutlela litsing tsa mantlha nakong ea metsotso e 30 eo ho sa kang hoa hloaetsoa (sampole 9 le 10). Ha ho khutlisoe hape ea 1 ea basali ka mora skrineng (sampole 11) kapa monyetla oa ho sebelisana 'meleng, empa ntle le ho nyoloha (sampole 12), maemo a phahameng a DA a amanang le boleng ba bobeli ba motheo (sampole 10). Boteng ba 2 ea basali kamora skrineng (sampole 13) e hlahisitse keketseho e nyane ea DA efflux (12%) ho tloha boleng ba boraro ba mantlha (sampole 12) e sa fihletseng bohlokoa ba lipalo. Ts'ebetso e nchafalitsoeng le basali ba 2 e hlahisitse keketseho ea bohlokoa (34%) (p <0.05) ho DA efflux nakong ea sampole ea pele ea ho kopitsa (sampole 14). Leha boits'oaro bo fokolang ba ho qopitsa bo ile ba tsoela pele ho feta lisampole tse tharo tse latelang, likhakanyo tsa DA li ile tsa theoha ho fihlela litekanyetso tsa mantlha (disampole tsa 15-17). Ikemetseng t Liteko tse entsoeng har'a sampole ea "baseline" (ke hore, 1, 10, le 12) li bonts'a hore boleng bona bo ne bo sa fapana haholo.

Liratseng tse tharo tse qalileng ho kopitsoa ha 1 ea basali e ne e etsoa bocha, likakanyo tsa NAC DA li ile tsa eketseha ha 1 ea basali e ne e le teng ka mora skrineng (mefuta, 25-47%), e amanang le sampole feela pele a hlaha botšehali. Keketseho ena, leha ho le joalo, e etsahetse feela ha boitšoaro ba thobalano bo le matla mme bo lebisa ho emeng.

Liphetoho tsa bohlokoa ka kakaretso ho DOPAC [F_(11,44) = 9.57; p <0.001] le HVA [F_(11,44) = 12.47; p Li-concentrations tsa <0. 001 li fumanoe ho arabela basali ba 1, empa eseng basali 2. Mefuta ea Metabolite e eketsehile hanyane (+ 15% maemong ka bobeli) nakong ea tlhahiso ea 1 ea basali ka mora skrineng (sampole 2), empa sena se ne se sa bohlokoa ka lipalo. Leha ho le joalo, ho bile le keketseho e kholo mehopolong ea DOPAC le HVA nakong ea ho kopitsa (mehlala ea 3-8), e fihlelang litekanyetso tse holimo (+80 le + 86%, ka ho latellana; p <0.01) kamora 60 min (sampole 6 maemong ka bobeli). Le ha metheo ea metabolism e fokotsehile nakong ea ho se sebetse ka thobalano qetellong ea ho kopana le basali ba 1 (disampole tsa 9 le 10), likhakanyo li ntse li lula li phahame mabapi le metheo ea mantlha (p <0.05 maemong ka bobeli). Ts'ebetso e ncha ea basali ba 1 ka mora skrineng (sampole 11), phihlello ho 1 ea basali kamora ho tlosoa ha skrine (sampole ea 12), le ho hlahisoa ha basali ba 2 (sampole ea 13) ha hoa ka ha baka liphetoho liphetohong tsa metabolism. Ho nyoloha hanyane, empa ha ho na lipalo-palo, ho eketseha ha likhakanyo tsa DOPAC le HVA (+ 23% maemong ka bobeli) ho bapisoa le motheo (sampole 12) e tsamaellanang le ho qalella ho kopitsa le basali ba 2 (sampole 14). Keketseho ena e bile ea nakoana, leha ho le joalo, 'me ea hana ho latela litekanyetso tsa mantlha bakeng sa mehlala e meraro e setseng (15-17). Ikemetseng tLiteko tse entsoeng har'a sampole ea "baseline" (ke hore, 1, 10, le 12) li bonts'itse hore litekanyetso tsa bobeli le tsa boraro (mohlala 10 le 12, ka tatellano), leha li sa fapana ka e mong, li lula li phahamisitsoe haholo ha li bapisoa le sampole ea pele ea motheo. bakeng sa DOPAC le HVA (p <0.05 maemong ka bobeli).

Histology

Lipatlisiso tsa Microdialysis li ne li le teng ho NAC (sa feiga.2) ka bongata bo atolosang + 1.20 ho + 1.70 mm ho tloha bregma (shata e sephara). Ho ne ho e-na le phapang le sefofaneng se pakeng; Lintlha li bonts'a mehlala e tsoang likhetleng le maemong a tlase a NAC.

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Setšoantšo sa 2.

Sebaka sa li-Microbialysis probes kahare ho NAC ea likhoto tsa banna tse sebelisitsoeng tlhahlobo ea phello ea Coolidge. Likala tse koahetsoeng E lumellana le sebaka se senotsoeng sa membrane ea Microbalal phenes. Likarolo tsa boko ba mantlha li 'nile tsa boela tsa hlaha hoPaxinos le Watson (1986).

TŠOHLOA

Ka tumellano le litlaleho tsa pejana, liphetho tsa hona joale li bonts'a phetisetso e matlafatsang ea ts'oaetso ea DA e amanang le takatso ea lijo le likarolo tsa boits'oaro ba banna joalo ka tlhahlobo eaKa vivo microsalysis (Mas et al., 1990; Pfaus et al., 1990;Pleim et al., 1990; Damsma et al., 1992; Wenkstern et al., 1993; Fumero et al., 1994; Mas et al., 1995a,b,d). Ntle le moo, liphetho tsena li fana ka "neurochemical correlate" bakeng sa ho ikatisa ka tsa thobalano le tokiso e latelang ea kopelo ho araba mosali ea amohelang molaetsa (phello ea Coolidge). Lintlha tse teng hona joale li fana ka maikutlo a hore likarolo tsa ts'usumetso tsa mosali ea amohelang buka ea bocha li ka thusa ho eketsa phetiso ea NAC DA molekeng o motona oa thobalano, o ka amanang le ho nchafatsoa hoa boitšoaro ba thobalano. Sena se bonahala pele keketseho e nyane ho NAC DA nakong ea tlhahiso ea mosali e mocha ka morao ho skrini mme e etsahala ka mokhoa o kholisang e le keketseho e boletsoeng haholoanyane nakong ea ho qaptjoa bocha le 2 ea basali (sa feiga.1).

Ho ba teng ha mosali oa pele ea amohelang ka morao ho skrini ho felletse ka keketseho e matla ea takatso ea NAC DA efflux (44% ho tloha ho basement) e lekanang le se tlalehiloeng litekong tse fetileng ho sebelisa moralo o ts'oanang (30%, Pfaus et al., 1990; 35%,Damsma et al., 1992). Hape tumellanong le lithuto tsena e bile tlhokomeliso ea hore NAC DA efflux e ntlafalitsoe ho feta nakong ea tšebetso (ho> 95% kaholimo ho motheo oa teko ea hona joale). Le ha re ka sheba boits'oaro bo tlatselletsang joalo ka ha bo amahanngoa le tokollo e ntlafalitsoeng ea NAC DA (Wenkstern et al., 1993; Wilson et al., 1995), ho bohlokoa ho hlahlobisisa mantsoe a reng, “takatso ea lijo” le “aummisang” molemong oa boitšoaro ba thobalano. Le ha karolo eo mosali a leng teng ka mora skrineng e le takatso feela ea boiketsetso kapa boitokisetso, boits'oaro nakong ea karolo ea bohlophisi bo ke ke ba nkuoa e le ntho feela e kopantsoeng. Hobane "takatso ea lijo" e ka sebelisoa ho hlalosa boitšoaro bohle bo lebisang ho pheletsong ea boitšoaro bo susumetsang (boqapi), boits'oaro bo mantlha boo monna a bo bonts'ang ha a ntse a le sehlopheng sa "ho phethesetsa" bo hlalosoa hantle e le takatso ea lijo; e tona e sebelisa boholo ba nako ea eona le boiteko ba eona e phehella mosali ho etsisa. Ntlheng ena, re ka hokahanya phetisetso e matla ea NAC DA le Consummatory 'moho le likarolo tse matla tsa takatso ea boitsoaro ba setho sa botona.

Ho fihlella ea bobeli, mosali oa novel ho felletse ka ho kopitsoa bocha nthong e ngoe le e ngoe. Boithuto bo fetileng bo bontšitse hore boholo ba likhoto li lumelletsoe ho kopitsa ho satiety, li sebelisa protocol e tšoanang ea boits'oaro ho e sebelisitsoeng boitekong ba hona joale, ha li a ka tsa qalella ho tlohelana ha li ne li lekoa 24 hr hamorao (Lebōpo le Jordan, 1956). Ho ka etsahala hore ho ba teng hoa nalane ea matlafatso ea thepa ea basali ea 2, e kanna ea kenyelletsa lintlha tse tlatselletsang hammoho le lits'oants'o tsa pono le ho bala, ho felletseng ka ho kopitsoa bocha. Potso e khahlisang, e sa ntseng e lokela ho arajoa, ke hore na mochini o motona o khetholla mosali e motšehali le mosali eo a mo kopileng haufinyane tjena. Sebaka sa mochine ona se ka lula ka har'a sistimi e kholo. Ho tlalehiloe hore bots'epehi ba sistimi ena bo bohlokoa bakeng sa phello ea Coolidge ho hamsters (Johnston le Rasmussen, 1984). Sisteronasal-accessory olildory system, leha ho le joalo, eo ho eona ho hlalositsoeng ts'ebetso ea memori ea pheromonal haufinyane ho litoeba (Kaba et al., 1994) hape ke moemeli ea ka sehloohong. Mabapi le hona, hoa bohlokoa hore ebe keketseho ea phetiso ea NAC DA e sebelisoa Ka vivo voltammetry ho likhoto tsa banna tse hlahisitsoeng le mealo e ileng ea pepesetsoa litoeba tsa basali ho estrus (Louillot et al., 1991; Mitchell le Gratton, 1992). Ntle le moo, ts'ebeliso ea K⁺ ka kotloloho ho mokelikeli oa mokelikeli oa ho hlatsoetsa oa "bulb" o fumanehang, hammoho le bulb ea litlolo tse fumanehang ka boeona, e ne e lekane ho eketsa phetiso ea NAC DA (Mitchell le Gratton, 1992).

Bout ea 15 ea pele ea ho qobelloa le 2 ea basali e ne e amana le keketseho e kholo ea NAC DA. Ho fapana le 1 ea basali, tšebelisano le 2 ea basali ha ea ka ea hlahisa keketseho ho NAC DA ea boholo bo ts'oanang nakong efe kapa efe ea mekhahlelo ea takatso ea lijo (12%). Keketseho ena e nyane ho NAC DA, leha ho le joalo, e lumellana hantle le boemo bo fokotsehileng ba boitšoaro ba thobalano bo bonts'itsoeng le 34 ea basali ha bo bapisoa le 2 ea basali. Mehlala ea Metabolite e lula e phahame nakong ea karolo ea satiety, e lebisang ho tsepamiso ea motheo ea basel (sampuli 1 le 10) tse ileng tsa phahamisoa haholo ho tloha boleng ba motheo ba mantlha (sampole 12).

Phokotso ea nakoana ho keketseho ea ho tsepamisoa ha DOPAC le HVA nakong ea ho kopitsa e lumellana le sebopeho sa bona e le li-metabolites tsa karolo ea motsoali, DA. Ho 'nile ha fanoa ka tlhahiso ea hore lintlha tse akaretsang tsa micodialysis metabolite, bonyane nakong ea boitšoaro bo sa sebetseng ka tlholeho, li fana ka index ea ts'ebetso ea neural (Damsma et al., 1992; Fumero et al., 1994). Taba ea hore methapo ea kutlo ea metabolite e lula e phahame esita le nakong ea ho se sebetse thobalanong ka teko ena, ha likhatiso tsa DA li ne li khutletse litekanyetsong tsa motheo, li beha lipelaelo ka tlhahiso ena.

Ho phahamisa ho phehellang ha metheo ea DA ea metabolite e bonoang tlhahlobong ena e supa sebaka sa medial preoptic area (mPOA) sa li-metabolites tsa DA tse hlokometsoeng litsing letsatsi la pele kamora hore ba qete ho satiation (Mas et al., 1995a,b). Ho phahamisoa ka mokhoa o tsitsitseng oa DOPAC le likhatiso tsa HVA ho NAC kapa mPOA ha se kamehla ho bonoang ha nako ea ho hola e le ea nako e telele, e khuts'oane ho feta nako e hlokoang ho fihlela satiation. Mohlala, liphuputso tse ngata li bonts'itse hore likhakanyo tsa DOPAC li ile tsa eketseha 'me tsa lula li phahame nakong ea ho kopitsoa empa tsa hana ho latela boleng ba mantlha hang hoba mosali a tlosoe (Pfaus et al., 1990; Pleim et al., 1990; Damsma et al., 1992;Hull et al., 1993; Wenkstern et al., 1993; Hull et al., 1995). Thutong ka Mas et al. (1995b), lintlha tsa basal extracellular tsa DOPAC le HVA ho mPOA li lutse li phahamisitsoe ka matsatsi a latellanang a 4 a tsamaellanang le nako ea ho se sebetse ka thobalano. Ka letsatsi la bone, pele liphoofolo li qalella ho li kopitsa, lintho tse ka sehloohong tsa metabolites li ne li le haufi le boleng ba ho boloka. Bangoli ba tšoantšitse phetoho ea methapo ea kutlo le e bonoang kamora ho tsamaisoa ha li-receptor blockers tsa DA (Zetterström et al., 1984; Imperato le DiChiara, 1985) mme re re boemo ba ho se kopanele thobalanong bo ka kopanngoa ka ho lokolloa ha prolactin, bo ka sebetsang e le "endo native neuroleptic" (Mas et al., 1995a,b,d). Ho hlakile hore tsamaiso ea neuroleptic e tsamaisana le keketseho ea likelello tsa extracellular metabolite le DA efflux (Zetterström et al., 1984; Imperato le DiChiara, 1985). Ka bomalimabe, Mas et al. (1995a,b) ha baa khona ho lemoha ho tsepamisa mohopolo ha mPOA DA. Phuputsong e teng hona joale, likhatiso tsa DA ho NAC li khutletse litekanyetsong tse ngata, athe tsepamiso ea DOPAC le HVA li ntse li phahamisitsoe. Mokhoa ona ha o lumellane le karolo ea setho sa methapo ea kutlo se sebetsang ho NAC ho etsa hore motho a be le takatso e matla ea thobalano.

Fuoa ho nka karolo ha mesolimbic DA neurons ho boits'oaro bo susumetsang (Fibiger le Phillips, 1986; Blackburn et al., 1992; Kalivas le al., 1993; LeMoal, 1995) le maikutlo a bona a susumetsang a pherekano ea tikoloho (Fabre et al., 1983; Schultz, 1992; Mirenowicz le Schultz, 1994), keketseho e bonts'itsoeng ea likakanyo tsa kantle ho Nac DA ha karabelo ea mosali e sa tsoa hlaha e lumellana le maikutlo a hore ts'ebetso tsamaisong ena ea DA e bohlokoa bakeng sa ho khutlisetsa boitšoaro ba thobalano. Ntle le moo, litlaleho tsa takatso ea lijo le e nyatsehang phetisong ea DA (Hull et al., 1993, 1995;Mas et al., 1995b; Sato et al., 1995) le tšebetso ea methapo (Shimura et al., 1994) ho mPOA ea likhoto tsa banna nakong ea boitšoaro ba thobalano e bonts'a hore sebopeho sena se kanna sa kenya letsoho ho ntlafatseng mokhoa oa ntlafatso oa phello ea Coolidge.

Ho tsamaisana le karolo e akaretsang bakeng sa sisteme ea mesolimbic DA ka boits'oaro bo susumetsang, ho thehiloe ka nepo hore likhatiso tsa extracellular tsa DA le tsona li phahamisoa pele, nakong, le hang ka mor'a tšebeliso ea lijo, ka ho khutlela litekanyetsong tsa motheo tsa ∼30 min hamorao (Wilson et al., 1995). Hoa tsebahala hore satiety e khothalletsoang ke lijo e susumetsoa ke maikutlo a eona. Batho le liphoofolo ba hana lijo tse ba fepelitsoeng ka tsona hore li satiety le ho ja lijo tse ling tse sa jelloang (Rolls, 1986). Sena se hlahisa potso ea hore na boleng ba DA ba tsoang kantle ho naha ba tla eketseha ka mokhoa o ikhethileng ka tlhahiso ea mofuta oa lijo, empa eseng ka lijo tse sebelisoang haufinyane ho satiety ka mokhoa o makatsang ho se tlalehiloeng thutong ea hona joale moelelong oa tšusumetso ea thobalano. Haeba ho netefalitsoe, kamano ena e akaretsang lipakeng tsa maikutlo a meputso ea tlhaho, satiety, le phetisetso ea mesolimbic DA e ka bolela karolo e bohlokoa bakeng sa sisteme ena mo taolong ea lits'ebetso tse susumetsang, pherekano ea eona e ka lebisang khatellong e kholo ea ho ja le ts'ebetso ea thobalano. .