mohloli o moholo
Lefapha la Pharmacology le Cancer Biology, Setsi sa Bongaka sa Duke University, Durham, NC 27710, USA. [imeile e sirelelitsoe]
inahaneloang
Bocha ke mocha oa ntlafatso oa nako eo bana ba bang ba fetoha ba baholo kelellong, 'meleng, li-hormone le sechabeng. Ntlafatso ea boko maemong a bohlokoa e ntse e tsoela pele. Bacha ba ipeha kotsing 'me ba batla lintho tse ncha ebile ba na le liphihlelo tse ntle haholo ho feta batho ba baholo. Khethollo ena ea tlhaho e ka lebisang liketsong tse kotsi joalo ka tšebeliso ea lithethefatsi. Boholo ba bokhoba ba lithethefatsi bo qala nakong ea bohlankana le bosholu ba ho sebelisa lithethefatsi ho amana le sekhahla se seholo sa ts'ebeliso e mpe ea lithethefatsi le ho its'etleha. Liphetoho tsa li-hormone tsa ho kena bohlankaneng li kenya letsoho phetohong ea 'mele, ea maikutlo, ea kelello le ea kahisano nakong ea bohlankana. Liketsahalo tsena tsa li-hormone ha li etse feela hore maemo a tšebetso a ho beleha le ho hlaha ha litšobotsi tsa botona le botšehali. Ba kenya letsoho ponahalong ea liphapang tsa botona le botšehali ka mekhoa eo e seng ea botona le eona. Phapang pakeng tsa thobalano mekhoeng ea tšebeliso ea lithethefatsi ke e 'ngoe ea tse latelang. Boholo ba botona ba ts'ebeliso ea lithethefatsi ka kakaretso bo hlahella qetellong ea bocha, ha banana ba nts'etsapele tsoelo-pele e potlakileng ho tloha ts'ebeliso ea pele ho isa ho ts'epahalong (telescoping) e emelang tlhekefetso ea basali. Phapang pakeng tsa thobalano mekhoeng e mengata e kenyeletsang ts'ebeliso ea lithethefatsi e hlahisitsoe ka mabaka a bophelo le setso. Phapang e nyane ea tšebeliso ea lithethefatsi pakeng tsa bashanyana le banana ba lilemong tsa bocha e tšehetsa taba ena. Leha ho le joalo, liphapang tse ling tsa botona le botšehali tse tlokotsing ea ho lemalla li bontša liphapang tsa biologic makaleng a bokong a kenyellelitsoeng temeng. Morero oa tlhahlobo ena ke ho akaretsa tlatsetso ea phapang ea thobalano tšebetsong ea litsamaiso tsa dopamine tse bohlokoa ho matlafatsa, ho akaretsa ka bokhutšoanyane liphetoho tsa boits'oaro, tsa methapo ea kutlo le tsa anatomical mesebetsing ea boko dopaminergic tse amanang le bokhoba bo etsahalang nakong ea bocha le ho hlahisa hona joale. liphumano tse ncha mabapi le ho hlaha ha phapang ea thobalano mosebetsing oa dopaminergic nakong ea bohlankana.
Copyright 2009 Elsevier Inc. Litokelo tsohle li sirelelitsoe.
Selelekela
Nako ea bocha ke monyetla o moholo oa ntlafatso ea lefu le lemaletseng. Hoo e batlang e le motho e mong le e mong ea sebelisang lithethefatsi o na le tsebo ea hae ea pele ea lithethefatsi tse lemalloang bongoaneng. Tšebeliso ea pele ea lithethefatsi tse lemalloang (ka tloaelo koae, joala kapa matekoane) e etsahala hoo e ka bang kamehla pele ho lilemo tsa 21, 'me ts'ebeliso e mpe ea lithethefatsi e qala, e ba kapele le ho feta le ho ba matla le ho feta.Essaf et al. 1989; Myers le Andersen 1991; Clark et al. 1998; Brown et al. 2008; Windle et al. 2008). Nako ea bocha ke nako ea phetoho e kholo - bana ba holima 'mele, maikutlong le sechabeng. Kholiso ea methapo ea methapo e ea sethaleng sa bohlokoahali, 'me liphetoho tsa ho fetoha ha mmele nakong ea bokhachane li ntse li tsoela pele. Tlhahlobo ea hajoale e sebetsana le tlatsetso ea phetoho ea bongoaneng lithutong tsa boits'oaro le mekhoa ea methapo ea kutlo e bohlokoa haholo bakeng sa nts'etsopele ea bokhoba ba lithethefatsi. Re shebile lintlha tsa biologic (nts'etsopele ea li-circuits tse khethehileng tsa neural) ho fapana le lintlha tsa maemo a bophelo tse kang karolo ea bong le tšusumetso ea lithaka e le karolo ea tlhekefetso ea lithethefatsi. Lingoliloeng tse pharalletseng mabapi le ho qetela li se li fumaneha (Dakof 2000; Waylen le Wolke 2004) ha mabaka a biologic a susumetsang bofokoli bo ikhethang ba bong bo sa buuoe haholo. Tlhahisoleseling eo re e hlahlobang e bonts'a hore ho ba kotsing ea ho lemalla bokhobeng nakong ea bohlankana ho bonts'a mesebetsi ea boko ba bongoana bo ikemetseng, le hore liphetoho tse bang teng maemong a fapaneng a tlhekefetso ea bongaka bakeng sa likarolo tse fapaneng tsa tlhekefetso tse hlahang qetellong ea bocha.
Likarolong tse latelang re tla hlahloba liphapang tsa tlhekefetso ea tlhekefetso ea lithethefatsi, babuelli ba bohlokoa ba li-endocrine tse fumanoeng mehlaleng ea liphoofolo, tšebeliso ea boitšoaro e ntlafatsang kotsi ea bokhoba ho isa lilemong tsa bocha, nts'etsopele ea bongoaneng ea methapo ea methapo ea methapo e amanang le basal ganglia le pele. cortex e sebelisang matlafatso ea ts'ebeliso ea lithethefatsi le hore na ho kena bohlankaneng ho ama mekhoa ena joang. Qetellong, re tla fana ka datha tse ncha tsa pele mabapi le ho hlaha ha phapang ea thobalano mosebetsing oa dopaminergic nakong ea bohlankana. Khaolo ena e phethela ka ho bua hakhutšoanyane ka mesebetsi e 'maloa e fapaneng ea bohloeki e kenyeletsang ts'ebetso e phahameng, taolo ea boits'oaro ba maikutlo le maikutlo a khatello ea maikutlo tse bohlokoa bakeng sa ts'ebeliso ea lithethefatsi empa li sa sebetse nakong ea bongoana. Tsena li emela sepheo sa bohlokoa bakeng sa lipatlisiso tsa nako e tlang.
Karolo ea 1: Thobalano, Gonadal Steroids le Bokhoba ba Batho ba baholo
Phapang Litabeng tsa Thobalano le Keketso ea ho Lemalla
Phapang lipakeng tsa Tlhekefetso ea Lithethefatsi ho Batho
Phapang ea botona le botšehali ka kutloisiso ea lithethefatsi, mekhoa ea tšebeliso ea lithethefatsi le karolo ea li-hormone tsa ho ikatisa ho phapano tsena li sekasekoe lingolong tse fetileng ho Buka mme ka hona tsena li tla akaretsoa hanyane feela mona. Ho na le liphapang tse peli tsa thobalano ka tšebeliso e mpe ea lithethefatsi bathong ba batho ba tlalehiloeng ka mokhoa o fapaneng. Taba ea mantlha, banna ba baholo ba bangata ba sebelisa lithethefatsi tse lemalloang ho feta ba batšehali ho feta litlelaseng tse ngata tsa lithethefatsi, ho kenyeletsoa joala, psychostimulants le narcotic (NHSDUH 2007; Tetrault et al. 2008). Leha ho le joalo, basali ba eketsa ho lemalla kapele, ba bonts'a "telescoping" lipakeng tsa ts'ebeliso ea mantlha ea lithethefatsi tse kenyeletsang joala, psychostimulants le li-narcotic mme ba na le ts'oaetso e phahameng ea lefu la kelello, nalane ea tlhekefetso ea mmele kapa thobalano (Ross et al. 1988; Brady et al. 1993; Brady le Randall 1999; Van Etten et al. 1999; Brecht et al. 2004; Diala et al. 2004). Leha ho le joalo, liphapang tsena li fokotseha ka potlako, kaha ho fetoha ha maemo a bophelo le setso ho susumetsa ka matla boitšoaro ba lithethefatsi. Ho na le ngangisano e kholo empa leseli le fokolang la konkreiti mabapi le karolo ea lintho tsa biologic ho e 'ngoe ea liketsahalo tsena.
Phapang ea Thobalano ho Tsamaiso ea lithethefatsi lithutong tse seng tsa batho
Phapang pakeng tsa botona le botšehali ho tlokotsing ea ho lemalla e bile tloaelo ho liphoofolo. Tsena li boetse li kentsoe lihloohong tse fetileng bukeng ena mme ke litaba tse bohlokoa feela tse amanang le bocha tse tla boleloa mona. Re tla akaretsa lingoliloeng tse khuts'oane ho li-primates tse seng tsa batho pele, ebe lingoliloeng tse pharalletseng tse sebelisitseng meetso ea litoeba.
Lingoliloeng tse mabapi le phapang ea thobalano tsa ho iphekola hoa lithethefatsi lithutong tseo eseng tsa batho li qalile li hlahlojoa hape (Lynch et al. 2002; Carroll et al. 2004), empa lintlha tse ling tsa bohlokoa li tla hlahisoa mona. Liphumano li fapana ka lithethefatsi le ka liteko tsa tlhahlobo. Le ha lithuto tse ngata tsa boits'oaro tse entsoeng lithutong tseo eseng tsa batho li kenyeletsa banna le basali, ke ba fokolang ba sebelisang lipalo tse kholo ho lekana ho bona phapang ea thobalano. Liphumano tsa ethanol li hlile lia hanyetsana. Phapang ea botona le botšehali ea ho inkela tsamaiso ea ethanol-self ha e ea ka ea bonoa lithutong tse seng tsa batho (Grant le Johanson 1988). Basali ba tlalehiloe hore ba noe ethanol e ngata tlasa maemo a ho se noe mahala empa ba le tlasana maemong a ts'ebetso (Juarez le Barrios de Tomasi 1999; Vivian et al. 2001). Ho nahanisisa ka phapang lipakeng tsa taolo ea koae ka lebaka la tekanyetso, thobalano le maemo a ho ea khoeling ho bontšitse hore litšoene tsa basali tse tšehali li tla sebetsa ho ea hola ka tekanyo e tsoelang pele nakong ea potoloho ea potoloho, empa ho seng joalo banna le basali ba arabela. ka mokhoa o ts'oanang (Mello et al. 2007). Litšoene tse tšehali li tlalehiloe li sebelisa phencyclidine e fetang ea ba batona (Carroll et al. 2005). Ka kakaretso, thuto ea ho fapana ka thobalano ho boitaolo ba lithethefatsi lithutong tse seng tsa batho ha e ea lekana ho fana ka tšobotsi efe kapa efe e hlakileng.
Phapang Litabeng tsa Thobalano Tlokotsing ea Keketseho ho Lisebelisoa tsa Rodent
Boholo ba lithuto tse hlahlobang phapang ea thobalano li sebelisa litoeba leha ho na le sengoloha se ntseng se hola se nang le litloholoana tseo eseng tsa batho. Mefuta ea liphoofolo ea litlamorao tse matlafatsang tsa lithethefatsi tse lemalloang e kenyelletsa ts'ebetso ea locomotor le maikutlo a eona, boikhethelo ba sebaka (CPP) le boitaolo. Ts'ebetso ea locomotor e hakanya kutloisiso ea ts'ebetso ea li-neuron tsa dopaminergic tse kenang phatleng ka lithethefatsi tse tlatsetsang empa ha li fane ka tekanyo e tobileng ea litlamorao tse matlafatsang. CPP e fana ka tlhahlobo e hlakileng haholoanyane ea litlamorao tse matlafatsang tsa lithethefatsi, 'me tsamaiso ea boits'oaro e fana ka "standard" ea khauta ea hona joale ea lithethefatsi tsa boithaopo. Tsena kaofela li fane ka leseli le itseng mabapi le ho hlaha ha phapang ea botona le botšehali litlamorao tsa lithethefatsi tse lemalloang tse etsahalang nakong ea bocha hobane mehato ena kaofela e matla.
Ho hlohlelletsa batho ka mokhoa o ts'oanang, sensorization ea locomotor, CPP le ho iphumanela ho itaola ha li-psychostimulants, li-narcotic, nicotine le ethanol li etsahala ka potlako, ka tekanyetso e tlase le / kapa li kholo haholo ho basali ho feta ba batona (Donny et al. 2000; Carroll et al. 2004; Hu et al. 2004; Chaudhri et al. 2005; Craft 2008; Yararbas et al. 2009). Nakong ea phihlello e khutšoane, ho arabela ka tekanyo e tsitsitseng, basali le banna ba iphelisa ka palo e lekanang ea cocaine (Caine et al. 2004). Leha ho le joalo, basali ba tla sebetsa ka thata bakeng sa li-psychostimulants tlasa lebelo le tsoelang pele, ba eketsa tšebeliso ka potlako le ho tobetsa bar ho feta nakong ea ho timela ho feta banna (Lynch et al. 2002; Carroll et al. 2004; Lynch 2006; Quinones-Jenab 2006; Becker le Hu 2008). Liphumano tsa morao-rao li fetoletsoe ho bontša hore tšusumetso ea ho sebelisa lithethefatsi e matla ho basali. Nakong ea ho oela hape ho tsamaiso ea koae, koae e bapisoa le tse tona kamora cocaine ha li ntse li bontša ho khutlisetsoa hofeta nakong eo li oelang hape ka molatsoana oa cocaine (Fuchs et al. 2005). Litšobotsi tsena tsa morao-rao ho nahanoa hore ke mohlala o motle oa ho sebelisa lithethefatsi tse bohlokoa bakeng sa bokhoba ba batho ho fapana le ho itaola habonolo.Vanderschuren le Everitt 2004). Phapang pakeng tsa thobalano maemong a fapaneng a taolo ea boits'oaro le eona e tlalehiloe. Ts'ebetso ea boithatelo ba nicotine e angoa haholo ke ts'usumetso e seng lithethefatsi ho basali ho feta banna mme e arabela ka nako ea nako ea ha nako e felile 'me nakong ea ho timela e kholo ho basali ho feta banna.Chaudhri et al. 2005). Liphapang tsena li ka bonts'a phapang ea thobalano taolong ea boitšoaro ba motho ea sebetsang. Ho fumaneha ha nikotine ho ka ama batho ka ho khetheha, hobane basali ba tlaleheloa ba ameha haholo ka mekhoa ea maemo e amanang le ho tsuba ho feta banna (Perkins et al. 1999). Ka kakaretso, basali ba bontša boits'oaro bo ka hlalosoang e le phetoho ea likarolo tse qobelloang ha motho a lemaletse joala kapele, joalo ka ha ho boletsoe bathong.
Litšusumetso tsa Gonadal Steroid mabapi le ho lemalla
Litšusumetso tsa Gonadal Steroid in Humans le li-primates tse e seng batho
Li-steroid tsa Ovarian ho nahanoa hore li susumetsa litlamorao tsa lithethefatsi tse lemalloang ho basali, empa hangata ka litsela tse poteletseng. Mokhoa o mong o sebelisitsoeng ho bonts'a litlamorao ke ho lekanya litlamorao tsa lithethefatsi kapa tšebeliso ea nako eohle ho ea matsatsing. Basali ba na le litlamorao tse kholo tsa lithethefatsi tse lemalloang nakong ea kemolo ea menstrual (Terner le de Wit 2006). Leha ho le joalo, ho na le mekhelo e hlokomelehang ho kenyelletsa ethanol, eo litlamorao tsa eona kapa tšebeliso e sa fetoheng ka mokoloto oa khoeli.Sofuoglu et al. 1999; Holdstock le de Wit 2000; Evans et al. 2002). Khatello ea litlamorao tse tlisoang ke koae ka progesterone e tlalehiloe lithutong tse 'maloa (Sofuoglu et al. 2002; Sofuoglu et al. 2004; Evans 2007). Litlhokomeliso tsena li qalile lithuto tsa tšebeliso ea kalafo e ka bang teng bakeng sa progesterone, e ka 'nang ea thusa lipakeng tsa litlamorao tse fokolisitsoeng nakong ea karohanyo ea potoloho. Liphumano tsena li tšohloa nako e telele kae kapa kae bukeng ena.
Litšusumetso tsa Gonadal Steroid ho Li-Behaviors tse Tlatsehang ho Mehlala ea Rodent
Lingolo tse pharalletseng tse tsoang lithutong tse entsoeng ka marang-rang li ts'ehetsa karolo ea ts'ehetso bakeng sa estradiol ho itaola ea lithethefatsi tse 'maloa, le karolo e hatellang bakeng sa progesterone. Estrogen e nolofalletsa ho fumana, ho eketsa ho arabela ka karolelano e tsoelang pele, 'me e ntlafatsa ho arabela nakong ea ho ts'oaroa ke ts'usumetso ea lithethefatsi leha litlaleho tse mpe li le teng (Grimm le Bona 1997). Ka lehlakoreng le leng, progesterone e hatella mekhoa ena e tšoanang (Feltenstein le Bona 2007; Feltenstein et al. 2009). Karolo ea li-steroid tsa testicular ha e kholoe. Ho kenyelletsa likhoto tsa banna ha ho fetole ho lokolloa ha dopamine ea psychostimulant kapa boitšoaro bo potolohileng ka mor'a amphetamine (Becker 1999) kapa ho fetola tsamaiso ea koae ea koaeHu le Becker 2003; Hu et al. 2004). Leha ho le joalo, liphuputso tse ling li bonts'a hore ho lahla likhoto tsa banna ho baka keketseho e potlakileng ea phokotso ea cococaine e matlafalitsoeng (Nako e telele le al. 1994; van Luijtelaar et al. 1996; Walker et al. 2001). Ka kakaretso, li-steroid tsa ovary li fetolela boits'oaro bo amanang le ts'ebeliso ea lithethefatsi haholo: estrogen e tsoella e ntlafatsa boits'oaro ho likhoto tse amanang le bokhoba, ha progesterone e hatella mekhoa e ts'oanang. Testosterone e sa sebetse kapa e hatella hanyane boits'oaro bo tšoanang.
Litlamorao tsa Gonadal Steroid Mesebetsing ea Dopaminergic E Arohane le bokhoba ba ho lemalla
Dopamine le Matlafatso
Litlamorao tsa steroid ea Gonadal ho tsamaiso ea lithethefatsi e aroloa ka karolo e itseng ka litlamorao ho li-neuron tsa dopaminergic. Li-neuron tsa dopaminergic tse projeke ho tloha sebakeng se tebileng sa nigra le sebakeng sa ho kenella ka mokokotlong oa caudate, li-nucleus accumbens (dorsal le ventral striatum) le frontort cortex li bapala karolo e hlahelletseng ho matlafatsong e tloaelehileng le ho qala ts'ebeliso ea ts'ebeliso ea lithethefatsi ho liphoofolo tse kholo mohlomong le phetoho. ho sebedisa tloaelo (Le Moal le Simone 1991; Kalivas le O'Brien 2008; Carlezon le Thomas 2009; Dalley le Everitt 2009). Lithethefatsi tsohle tseo batho ba itlhahisang ka tsona ba kenya tšebetsong methapo ena ea dopaminergic, ho kenyeletsa le nicotine, joala, opiates le li-psychomotor tse hlasimollang joaloka cocaine le amphetamine (Di Chiara le al. 2004). Liphetoho tsa nts'etsopele ea li-hormone le li-gonadal steroid li-hormone ho dopaminergic neurons tse projeke e tsoang sebakeng sa substantia nigra le ventral e tla ba sepheo sa tlhahlobo ea hona joale. Le ha gonadal steroids e fetolela ka matla hypothalamic dopaminergic neurons e laolang ho lokolloa ha li-hormone le boitšoaro ba thobalano (Hull le al. 1999; Ben-Jonathan le Hnasko 2001; Dominguez le Hull 2005), tlatsetso ea li-neurons tsena tsa bokhoba ba lithethefatsi ha e so ithutoe haholo mme e ke ke ea buisanoa mona.
Pharologanyo ya thobalano mo tirisong ya Dopaminergic mo bathong le mo bathong ba e seng batho
Phapang pakeng tsa thobalano le tšebetso ea dopaminergic e teng e ka bakang karohano ea thobalano tsamaisong ea lithethefatsi (e hlahlojoe ke Jill Becker bukeng ena, hape le (Becker 1999; Becker le Hu 2008; Morissette et al. 2008). Lingoliloeng tse fumanehang ka batho le li-primates tse seng tsa batho li tšohloa pele, li lateloa ke tlhahisoleseling mabapi le litoeba.
Le ha phapang ea thobalano ho neurochemistry le neuroanatomy ea forebrain dopaminergic neurons e sa ka ea ithutoa ka botlalo bathong le litoneng tseo eseng batho, bopaki bo bong bo bontša phapang ea thobalano e teng. Lintlha tsa mantlha li tsoa liphuputsong tsa kotsi ea mafu: basali ha ba na monyetla oa ho ba le lefu la Parkinson, 'me ba e etsa hamorao.Baldereschi et al. 2000; Wooten le al. 2004). Lithuto tsena li bontša hore dopaminergic innervation ea basal ganglia e ka fapana ho banna le basali. Leha ho le joalo ho bile le boithuto bo fokolang ba thuto ea potso ena. Lithuto tse entsoeng tsa ho lokolloa ha dopamine li tsoakiloe: lithuto tse ling li bontša hore basali ba bonts'a tokollo ea dopamine e kholo ho arabela li-psychostimulants, mme ba bang ba bontša hore banna ba etsa joalo (Munro et al. 2006; Riccardi le al. 2006). Ka hona, lingoliloeng ha li khethollehe ka mofuta oa ho fapana ha thobalano le tšebetso ea dopaminergic bathong.
Phapang ea Thobalano Mosebetsing oa Dopaminergic ho Rodents
Phapang pakeng tsa thobalano mesebetsing ea presynaptic (ho lokolloa ha dopamine) le mosebetsi oa postynaptic (polelo le taolo ea li-dopamine receptors) li bontšitsoe haholo. Tsena li ithutoe haholo ka litoeba. Ho 'nile ha etsoa tlhahiso ea hore ho kopantsoe ho lokolloa ha basal dopamine, bokhoni ba ho susumetsa ho lokolloa ha dopamine le kutloisiso ea li-receptor li kenya letsoho karabong e ntlafalitsoeng ea dopamine ea basali (Castner le Becker 1996) e fetolelang tšebetsong e ntlafalitsoeng ea boits'oaro (Becker le Hu 2008). Ho lokolloa ha dopamine ea basal ha ho tšoane ho ba batona le ba batšehali: liphuputso tse sebelisang maqhubu a tlase kapa maqhubu a theohileng ka sekhahla se ka reng li-cyclic voltammetry li bontša hore banna le basali ba boemong bo batlang bo tšoana le ba dopamine ha ba le mosesane ka tsela e hlakileng.Becker le Ramirez 1981b; Castner le al. 1993; Walker et al. 2000; Walker et al. 2006). Ka mokhoa o ts'oanang, lipalo tsa li-receptor tsa D1 le D2 ho dorsal le ventral striatum li ts'oana hantle ho banna le basali, 'me phuputso e le' ngoe e tlaleha le boholo ba li-receptor tsa D1 ho ba batona (Becker le Ramirez 1981b; Festa et al. 2006). Leha ho le joalo, basali ba bontša dopamine e sa khaotseng e phahametseng ka lebaka la ho susumetsoa ke motlakase kapa li-psychostimulants ho dorsal striatum. Laborator ea rona e bonts'itse hore ts'ebetso e phahameng haholo, e hlahisoang ka motlakase ka d femal striatum ho basali e batla e imena habeli e hlokometsoeng ho banna (Walker et al. 2000). Liphumano tsena li lumellana le tlaleho ea hore amphetamine e baka likarabo tse kholo ka ho fetisisa tsa c-fos (karabelo ea pele ea liphatsa tsa lefutso e bonts'a kakaretso ea tšebetso ea pele le ea post-synaptic) ho basali ba proestrous (Castner le Becker 1996). Ho phatlalalitsoe hore litoeba tsa basali tse maemong a phahameng a estrogen li bonts'a likarabo tsa dopaminergic lithutong tsa pharmacologic tse fetang tsa banna hammoho le tsa basali libakeng tse ling tsa endocrine.
Lingolo tse pharalletseng li tšehetsa karolo ea bohlokoa bakeng sa estrogen ho matlafatseng tšebetso ea pele le ea postynaptic dopaminergic. Ho lokolloa ha dopamine ea estrogen, ho eketsa palo ea li-receptor tsa D1 le D2 ka ho liehisa litheko tsa ho senyeha ha li-receptor le ho ntlafatsa tlhahiso ea DAT (Morissette et al. 1990; Levesque le Di Paolo 1991; Morissette le Di Paolo 1993; Morissette le Di Paolo 1993; Becker le Hu 2008; Morissette et al. 2008). Ho kenyellelitsoe li-hypotheses tse ngata ho hlalosa hore na estrogen augments dopaminergic e sebetsa joang. Khopolo-taba e 'ngoe ke hore estradiol e fokotsa thibelo ea "GABA-mediated inhibition" ea dopaminergic terminals (Hu et al. 2006). Ho fapana le hoo, lithuto tse ngata tsa banna ba baholo li bontša hore testosterone ha e laole mosebetsi oa dopaminergic ho dorsal kapa ventral striatum (Becker 1999; Becker 2009). Leha ho le joalo, li-circuits tsa cortex dopaminergic tsa frontal tse bohlokoa bakeng sa ts'ebetso ea botsamaisi le mohopolo oa ho sebetsa li tsamaisoa ke androgen (Adler le al. 1999; Kritzer 2000; Kritzer le ba bang. 2001; Kritzer 2003; Kritzer le ba bang. 2007), mme lits'ebetso tsena li ka kenya letsoho haholo ho ba tlokotsing ea ho lemalla. Ketso ea Androgen mesebetsing ena ea boko e bontša lekhalo la bohlokoa tsebong ea rona ka litlamorao tsa gonadal steroid ka boits'oaro bo bobebe.
Liphello tsa Steroid ea Gonadal ho Anatomy ea Dopamine Systems
Litlamorao tsa Gonadal Steroid Hormone ho Anatomy of Dopamine Systems in Humans and Non-Human Primates
Li-steroid tsa Gonadal li ka susumetsa morphology ea dopaminergic neurons hammoho le polelo ea bohlokoa ea liprotheine tsa dopaminergic le taolo e amanang le tokollo ea dopamine. Bopaki bo kholisang bo tšehetsang monyetla ona e ne e le tlaleho ea hore ovariectomy ea li-primates tsa basali e bakile ho fokotseha ho sa feleng ha nomoro ea sele ea dopamine ho nigra eaantiene e ka thibeloang ke phetoho ea estradiol (Leranth et al. 2000). Li-primates, estradiol le progesterone ka bobeli li eketsa khatello ea methapo ea methapo ea kutlo ea dopaminergic neurons libakeng tse ling ho kenyelletsa dorsolateral (libaka tsa setso sa kutlo) tsa dorsal striatum hammoho le cortex ea pele (Kritzer le Kohama 1998; Kritzer le ba bang. 2003). Estradiol e boetse e na le litlamorao tse sebetsang mabapi le ho lokolloa ha dopamine ka litšoene: ho khutlisoa ha estradiol ho litšoene tsa Parkinsonia ho ka ntlafatsa tokollo ea dopamine esita le ka mor'a nako e telele ea ho fokotsoa hoa estrogen (Morissette le Di Paolo 2009).
Liphello tsa Hormone ea Gonadal Steroid ho Anatomy ea Dopaminergic System ho Rodents
Liphuputso tse ngata li bontša hore estradiol e na le karolo ea trophic ea ho boloka li-neuropathy tsa dopaminergic, haholo-holo ha li araba likotsi tsa neurotoxic (Morissette et al. 2008). Boithuto ba morao-rao bo tsoang laboratoring ea rona bo bonts'itse hore litoeba tsa basali li na le li-neuron tsa dopaminergic ka bobeli sebakeng sa substantia nigra le ventral tegmental, le hore estradiol e boloka nomoro ea sele ea dopamine ho litoeba le litoeba haholoholo ka liketso ho estrogen receptor beta (Johnson 2009a). Lithuto tsa rona li boetse li khothalelitse karolo ea li-testosterone tsa li-testic mohlaleng ona, kaha ho lahleloa ha likhoto tsa banna ho bakile keketseho e sa lebelloang ea palo ea li-neurone tsa dopaminergic (Johnson 2009b). Leha lithuto tse ling li sa tlalehe phapang e joalo (Ho roka et al. 2006; McArthur et al. 2007), lithuto tsa morao-rao ha lia ka tsa sebelisa lipalo tse se nang boikaketsi, e leng maemo a thata ka ho fetisisa tšimong. Liphapang tsena ka palo ea li-neuron tsa dopaminergic li ka kenya letsoho liphapang tse tlalehiloeng ts'ebetsong ea dopaminergic kamora ho qhekella ha maemo a lihormone tsa gonadal steroid. Ka mokhoa o makatsang, phapang ea thobalano ho dopaminergic innervation ea dorsal le ventral striatum ha e so tlaleoe. Leha ho le joalo, dopaminergic innervation ea frontal cortex e ithutile, mme androgen e ka kenya letsoho haholo sebakeng sena. Kritzer o bontšitse hore androgen e fokotsa letsoalo la batho ba lefuang ka kotloloho ea litoeba (Adler le al. 1999; Kritzer 2000; Kritzer 2003).
Ho ba teng hoa taolo e matla ke estradiol le taolo e itekanetseng ea testosterone li lumellana le polelo e tlalehiloeng ea li-receptor tsa li-hormone tsa gonadal li-dopaminergic neurons. Peresente e kholo ea li-neurop tsa dopaminergic tse sebetsang ka har'a midbrain expression androgen receptors, athe ke liperesente tse nyane feela tse hlahisang e 'ngoe ea li-receptor tse ka sehloohong tsa estradiol (ERcy le ERβ) (Kritzer 1997; Creutz le Kritzer 2002; Creutz le Kritzer 2004; Kritzer le Creutz 2008). Liphapang tsena tsa anatomical li emela mokena-lipakeng oa bohlokoa oa litlamorao tsa li-hormonal mosebetsing oa dopaminergic. Li ka sebetsa ka ho khetheha joaloka babuelli ba liphetoho tsa ntlafatso.
Estrogen joalo ka mokena-lipakeng oa phapang ea thobalano le ho lemalla
Matlafatso ea ts'ebetso ea dopaminergic bokong ba letsoho ke estradiol e hlahisitse khopolo-taba ea hore phello ena e baka phapang lipakeng tsa thobalano le taolo ea lithethefatsi mefuteng eohle ea liphoofolo tse anyesang.Lynch et al. 2002; Carroll et al. 2004; Lynch 2006; Becker le Hu 2008). Ho tloaelehileng ha ts'ebetso ena ho ka supa mokhatlo o hlophisitsoeng oa bohlokoa oa hore na tšusumetso e hokahane le boemo ba ho ikatisa joang ho ba batona le ba batšehali. Taolo ea li-neuron tsa dopaminergic tse hlahelletseng bokong ba mahe a mpa empa e se li-testicular steroids e nahanoa ho lumella banna ho batla balekane (ba sebelisa sisteme ena ea dopaminergic) ka nako efe kapa efe, athe basali ba mpa ba batla balekane ba thobalano ha ba emere (Becker le Taylor 2008) leha sena se ka 'na sa se bonts'e boikemisetso ba boitšoaro ba thobalano ka se (Paredes le Agmo 2004).
Phokotso e hlalositsoeng hantle ea ts'usumetso ea thobalano (hara likhaello tse ling) ho lefu la Parkinson le ho hlaha ha boitšoaro bo sa lokelang ba thobalano nakong ea kalafo le li-agonists tsa dopaminergic e fana ka maikutlo a hore dopamine e kenya letsoho ho boits'oaro bona bathong (Meko et al. 2008). Leha ho le joalo, tlatsetso e lekanyelitsoeng ea li-steroid tse khethehileng tsa gonadal ha e tsejoe ka mokhoa o ikhethang le lithuto tsa morao-rao ho batho li bontšitse hore hypogonadism e sitisitse ts'ebetso ea thobalano ho banna le basali, empa testosterone eo e tsosolositseng ts'ebetso ho banna empa estradiol ha e etse joalo ho basali (Czoty et al. 2009). Ho feta moo, lithuto tsa ho lokolloa ha dopamine ka har'a dorsal le ventral striatum ea batho li bontša phapang e sa lumellaneng ea thobalano. Ho phatlalalitsoe lithuto tse peli tsa tokollo ea dopamine ho batho tse tlalehang tse fumanoeng tse amanang le bong: e 'ngoe e tlaleha hore tokollo e ne e le kholo ho banna,' me e 'ngoe e le e kholo ho basali.Munro et al. 2006; Riccardi le al. 2006)
Li-steroid tsa Gonadal li boetse li laola tšusumetso ea thobalano lithutong le ha lithahasello tse seng tsa hormonal (sechabeng) li bapala karolo ea bohlokoa (Wallen le Zehr 2004). Li-primates tsa basali tse seng tsa motho li hokahanya boitšoaro ba thobalano le nako ea ho ea matsatsing (potoloho ea mahareng) e amanang le tsoalo e phahameng (Bonsall et al. 1978). Ntle le moo, ho lokolloa ha dopamine ho ka laoloa ke li-ovari tsa li-ovari ka li-primates tse seng tsa motho, joalo ka ha phuputso ea PET ea morao-rao e bonts'itse hore basal DA e lokolloe e ka ba tlase nakong ea luteal ho feta karolo ea follicular ho li-primates tse seng tsa motho.Schmidt et al. 2009).
Karolo ea 2: Bocha le Bokhoba ba Bokhoba
Nako ea bocha e ba Ntlha ea Bohlokoa ea Tlatsetso Bakeng sa Tlatsetso ho Batho
Bocha ke phetoho ea ho qetela ea tsoelo-pele e tšoaeang phetoho ea ho ba motho e moholo (Spear 2000; Windle et al. 2008). Molemong oa tlhahlobo ena, re tla sebelisa lilemo tse hlalositsoeng litekong tsena tse peli. Ka bathong, e qala ho tloha lilemong tsa 10-25. Nako ena ea lilemo e kholo ho feta kamoo ho tloaelo ho fanoang ka eona. Leha ho le joalo, liphuputso tsa morao-rao tsa monahano oa boko li bontša hore boko ha bo holile ka botlalo ho fihlela bohareng ba mashome a mabeli (Lenroot le Giedd 2006).
Ho phetheloa ha kelello le kholo ea nts'etsopele e kenella lipakeng tsa liphetoho tse kholo tsa setso le maemo sechabeng tse etsahalang ha bana ba fetola tšusumetso ea bona ho tloha lelapeng ho ea ho lithaka. Boithuto ba morao-rao bo bonts'itse hore sebopeho sa boko se tsamaisong ea ho qetela nakong ena. Bosholu ba litaba tsa botala bo oela, mohlomong bo bontša keketseho e nyarosang ea myelin le ha tšubuhlellano ea likarolo tsa boko ka bomong e fapana (Isralowitz le Rawson 2006; Paus et al. 2008; Giedd et al. 2009) le segokanyipalo sa synaptic se oela butle nakong ea bohlankana, bonyane ho li-primates tse seng tsa motho (Bourgeois et al. 1994).
Ts'ebetso ea Brain e boetse e phethela mehato ea hoqetela ea ntlafatso nakong eo mesebetsi e sebetsang e kang ho lieha ho khotsofatsa (Casey et al. 2000; Steinberg et al. 2008; Astle le Scerif 2009) le ho sebetsana le moputso le lintho tse khothatsang qetellong li holile qetellong ea bohlankana (Ernst et al. 2006; Ernst le Mueller 2008; Ernst le Fudge 2009). Ho se tiisehe ha ts'ebetso ea moputso ke dopaminergic system le li-circuits tsa cortical tse sitisang boitšoaro ho bohlokoa haholo bakeng sa ho ba tlokotsing ea ho lemalla bongoaneng. Boithuto bo bakoang ke batho bo bontša hore bacha ba ka ba le tjantjello ea ho fumana moputso, ba sa tsotelleng maikutlo a susumetsang ebile ba sa khone ho thibela likarabo hobane li-circuits tsa cortex tse laolang boitšoaro ha li hole ha li bapisoa le batho ba baholo.Crews le Boettiger 2009; Geier le Luna 2009). Ho batla ho potlaka le ho ts'oara ho phahame haholo lilemong tsa bocha (Spear 2000; Steinberg et al. 2008). Lingolo tse ngata li supa litšobotsi tsena tsa boitšoaro kapa likhopolo tse amanang le kelello tse amanang le "neurobehaisheral disinhibition" e le mabaka a bohlokoa a tlisoang ke kholo ea ts'ebeliso ea ts'ebeliso ea lithethefatsi, haholoholo lilemong tsa bocha.Dawes et al. 2000; Crews et al. 2007; E-et-et al. 2008; Perry le Carroll 2008; Crews le Boettiger 2009; Volkow et al. 2009). Ka bokhutšoanyane, boemo ba nts'etsopele ea bongo ea bongoana bo ka beha bacha kotsing ea tlhekefetso ea lithethefatsi ka mabaka a 'maloa: ba ka arabela mehopolong e khothatsang ho feta e susumetsang e khothalletsoang ke batho ba baholo, ba theola litlamorao tsa nako e tlang,' me ba batla ho susumetsa. Ho na le litlhahlobo tse 'maloa tse ntle sebakeng sena (Crews et al. 2007; Brown et al. 2008; Windle et al. 2008).
Bocha e le Sekhahla sa Tsoelo-pele ea Bokhoba ba ho Rera
Ka litoeba, nako ea bocha e qala ho tloha matsatsing a ho beleha (PN) 25 ho ea ho motho e moholo ea holileng ka PN60 (Spear 2000). Nako ena e kenyelletsa empa e sa thibeloe ho nts'etsopele ea "pubertal". Joalo ka batho, nts'etsopele ea boko e tsoela pele ho fihlela qetellong ea nako, 'me PN60 e lokela ho nkuoa e le nako ea pele ea tšebetso ea boko ba baholo e teng, mme ho ka etsahala hore mesebetsi ea morao-rao e ntseng e eketseha e holile ka tsela e itseng kamora ho qheleloa ka thipa (Rice le Barone 2000; McCutcheon le Marinelli 2009).
Le ha lingoliloeng tse mabapi le nts'etsopele ea boits'oaro li se ngata, ha ho nkuoa lilemo tse loketseng tsa ho ima kamora 'tsoelo-pele ea boits'oaro bo hlaha ho litoeba le ho batho nakong ea bohlankana. Ho nka likotsi le ho batla ho phahama ho phahame haholo ka litoeba, joalo ka ha li le ho batho (Spear 2000; Laviola et al. 2003). Lingoliloeng tse nyane empa tse ntseng li hlaha li ts'ehetsa matla a tšoanang a ho putsa ka lebaka la litla-morao tsa lithethefatsi tse lemalloang lilemong tsa bocha (Laviola et al. 2003; Schramm-Sapyta et al. 2009). Ho tloaelehileng ha lits'ebetso tsena ho fana ka maikutlo a hore meetso ea litoeba e ka fana ka sesebelisoa se bohlokoa sa ho hlahloba mekhoa ea boko e bohlokoa bakeng sa nts'etsopele ea bokhoba ba tahi.
Ka kakaretso, mekhoa e 'maloa e amehang ka matla kholisong ea phetoho ea bokhoba ba lithethefatsi ka potlako nakong ea bohlankana. Li-circuits tsa Neural tse kenyelletsoang ts'ebetsong ea moputso hammoho le tse laolang mesebetsi e metle tse sitisang boitšoaro e ka ba tsona li amehang ho feta tekong ea ho ba tlokotsing ea ho lemalla, kaha bacha ba kanna ba tsotella ho matlafatsoa, mme ba bonts'a bokhoni bo fokolang ba ho thibela likarabo tse ipapisitseng le liphetho tsa nako e tlang.
Ho Etsa Lintho Tse Amanang le Ho Lemaletse Bokhoba nakong ea bocha
Mefuta ea liphoofolo e fana ka leseli la bohlokoa mabapi le hore na boits'oaro bo amanang le bokhoba bo fetoha joang lilemong tsa bocha, joalo ka ha lithuto tsa liteko ho batho li sa sebetse hantle, 'me lithuto tsa tlhaho li ferekantsoe haholo ke maemo a thata a moruo, tikoloho le liphatsa tsa lefutso tse hlokang tlhahlobo e sa feteng boiphihlelo ba hajoale lekola. Bongata ba lithuto tsena li entsoe ka litoeba; lithuto tsena li tla hlahlojoa ka tlase.
Litšobotsi tse ntle tsa litloaelo tsa lithethefatsi tse ngata tse lemalloang li fetoha ha bacha ba se ba holile, 'me liphetoho li tloaelana le lithethefatsi bakeng sa boitšoaro bo itseng. Kgetho e le 'ngoe e ka ba ketsahalo ea maiketsetso, kaha liphetoho tse bang teng bonyenyaneng ba nako ea bocha ke tsona tse ikhethileng ka lithethefatsi. Lithuto tsena li hlahlojoa ke Schramm-Sapyta (Schramm-Sapyta et al. 2009). Amphetamine le methamphetamine li nolofalletsa batho ho tsofala lilemong tsa bocha ho feta batho ba baholo, athe maikutlo a ts'oaroang ke cocaine a ntse a le lilemong tsa bocha ho feta batho ba baholo. Nikotine ho tlalehiloe hore e fokotse kapa e eketsa mofuta oa tikoloho ka mokhoa o ikhethileng, ho latela tekanyo kapa mefuta ea tlasa thuto. Ho theoha ha koluoa ho bakoa ke kalafo ea nikotine ea litoeba, mme keketseho ena e fokola ho bacha.Lopez et al. 2003). Ho litoeba, nicotine e tlalehoa e eketsa pherekano, 'me bacha ba boemong bo tlase ba sa tsotelloe ke phello ena (Faraday et al. 2001).
Consomization sensomotor, eo ho nahanoang hore e bonts'a liketsahalo tsa neuroplastic nakong ea ts'oaetso ea lithethefatsi tsa lithethefatsi butle-butle, butle-butle li eketseha lilemong tsa bocha ka mor'a kalafo ka amphetamine, cocaine kapa methylphenidate: sensitization e tlase ha kalafo e qala nakong ea bongoana, e ba matla le ho feta nakong ea bocha empa e le kholo ho ho ba motho ea moholo ho feta lilemong tsa bochaKolta et al. 1990; McDougall et al. 1994; Ujike et al. 1995; Bowman et al. 1997; Laviola et al. 1999; Tylli et al. 2003; Frantz et al. 2007). Kgetho e le 'ngoe e kanna ea ba le maikutlo a latelang ho hlahisoa ha lithethefatsi tse le' ngoe, kaha laboratori ea rona e hlokometse ntlafatso ea kutlo ea tekanyetso e le 'ngoe ho bacha ha e bapisoa le batho ba baholo.Caster et al. 2007). Boitšoaro ba kelello ba Nikotine bo hlahisoang ke kalafo ea likhoto tsa lilemong tsa bocha ha bo na taba e fetang ea kalafo e tšoanang ea litoeba tsa batho ba baholo, le ha maikutlo a koahelang cocaine le amphetamine li ne li le kholo ho banna ba batona ho feta banna ba baholo.Collins le Izenwasser 2004; Collins et al. 2004; Cruz et al. 2005; McQuown et al. 2009).
CPP ea lithethefatsi tse lemalloang haholo ho kenyeletsa nicotine, cocaine le amphetamine li matlafatsoa nakong ea bocha.Vastola et al. 2002; Belluzzi et al. 2004; Badanich et al. 2006; Kota et al. 2007; Torres et al. 2008; Brenhouse le Andersen 2008a; Schramm-Sapyta et al. 2009; Shram le Le 2009; Zakharova et al. 2009) leha ho fumanoe tse fumanoeng tse hanyetsanang bakeng sa cocaine le amphetamine (Adriani le Laviola 2003; Tylli et al. 2003; Schramm-Sapyta et al. 2004). Lintlha tse loantšanang li teng bakeng sa ethanol CPP ka likhoto le litoeba (Philpot et al. 2003; Dickinson et al. 2009) le "cannabinoid agonist" WIN5512-2 e baka CPP ka tekanyetso e tlase ho batho ba baholo ho feta likhoto tsa bocha.Pandolfo et al. 2009). Ka kakaretso, CPP e ntlafatsoa ho bacha ha e bapisoa le batho ba baholo ha maikutlo a fokola liphoofolong tse tšoaroang khafetsa ka li-psychostimulants nakong ea bocha ho feta ba tšoaroang joalo ka batho ba baholo. Liphetho tsena tse fapaneng li bonts'a hore bacha ba phela le litlamorao tsa matla le methapo ea maikutlo, empa litlamorao li ka fokotsoa ke ba baholo ha ba pele ba ntse ba feteletsoa. Litlamorao tse matlafatsang tsa lithethefatsi tse lematsang haholo literekeng tsa bocha li ts'oana le karabelo e eketsehang ea moputso o tlalehiloeng kaholimo o hlokometsoeng ho batho le litoeba.
Tekanyetso ea ho lekola sekoloto sa lithethefatsi tsa tlhekefetso ke ho itaola. Boithuto ba liphoofolo boo ho ipusa ho qalang bocheng le ho ba motho e moholo ha bo bapisoa ho hlahisitse liphetho tse sa fetoheng bakeng sa lithethefatsi tse ling, empa lipatlisiso tse hanyetsanang tsa lithethefatsi tse ling. Ka kakaretso, ho iphumanela ho itaola hoa ethanol ho potlakile ho potlakang ho bacha (Bell et al. 2003; Brunell le Spear 2005; Doremus et al. 2005; Bell et al. 2006; Vetter et al. 2007). Ho fumaneha ka potlako ea ho itaola ka nicotine ho tlalehiloe ho bacha ho bapisoa le liphoofolo tse qalang ho itaola e le batho ba baholo (Chen et al. 2007; Levin et al. 2007) le litoeba tsa bocha empa e se batho ba baholo li tla noela ka boithaopo litharollo tse nang le nikotine (Adriani et al. 2002). Leha ho le joalo, bacha ba iketsetsa nikotini e nyane ho feta batho ba baholo ka linako tse batlang tsa ho matlafatsa, 'me ba bontša ho fela ka potlako le ho oela hanyane ho feta ba baholo (Shram et al. 2008; Shram et al. 2008). Tse ling tsa tsena tse sa lumellaneng litlalehong tsa ho itšunya-tšunya ha nicotine ho bacha le batho ba baholo li ka supa bohlokoa bo lekanang ba moputso le ho ikhula lilemong tse fapaneng. Le ha bacha ba tloaela ho ameha haholo ka litlamorao tsa nicotine (bona kaholimo), ba tloaetse ho bonts'a ho itšepa ho fokolang (O'Dell et al. 2004; O'Dell et al. 2006; Wilmouth le Spear 2006; O'Dell et al. 2007; Shram et al. 2008). Kamora nako, liphumano tse nang le boikoetliso ba koae e bile tse leka-lekaneng ka ho fetisisa. Leha ho fumaneha ka potlako ea boits'oaro ho hlokometsoe bonyane bakeng sa liphoofolo tse nang le khetho e tlase ea saccharin (Perry et al. 2007), liphuputso tse ling tse 'maloa li bonts'itse hore boits'oaro bo tsitsitseng ha bo fapana ho latela hore na ho itaola ho qala nakong ea bohlankana kapa botsofaling (Frantz et al. 2007; Kantak et al. 2007; Kerstetter le Kantak 2007; Li le Frantz 2009). Boholo ba lithuto tsena li sebelisa kemiso ea setso e tsitsitseng ea nako e sa lekeng hore na liphetoho tse bohlokoa li fetoloa kapa ho nyoloha li lekoa ka mofuta oa li-regimation.Vanderschuren le Everitt 2004). Ka kakaretso lingoliloeng li fana ka maikutlo a hore bacha ba ka ameha haholo ka litlamorao tse matlafatsang tsa tlhekefetso, empa ha ho na data e ntseng e le teng ea ho lekola hore na bacha ba eketsa ts'ebeliso le tsoelo-pele ea ts'ebeliso e qobelloang ho feta ea batho ba baholo.
Boemo ba mosebetsi oa Forebrain Dopaminergic nakong ea bocha
Karolo ea bohlokoa ea li-neurop tsa dopaminergic ho matlafatsong ea thobalano le lithethefatsi le liketsahalo tsa bohlokoa tsa phatlalatso tse qalang mohopolo oa thobalano li fana ka maikutlo a hore liphetoho tsa nts'etsopele tsa li-neurop tsa dopaminergic nakong ea ho kena bohlankaneng e ka ba ketsahalo ea bohlokoa bakeng sa ho ba kotsing ea tlhekefetso ea lithethefatsi. Boithuto bo bontšitsoeng ka holimo bo fana ka maikutlo a hore ts'ebetso ea li-dopaminergic neurons ka li-suppforcers tse kenyelletsang lithethefatsi e ka ba kholo nakong ea bohlankana ha e bapisoa le batho ba baholo. Karolong e latelang, re tla hlahloba se tsejoang ka ho kenella ka har'a dopaminergic neurons mme re hlahise data e ncha ka ho hlaha ha phapang ea thobalano mosebetsing oa dopaminergic.
Boemo ba mosebetsi oa Forebrain Dopaminergic in Humans
Lisebelisoa tsa dopaminergic tse e seng tsa batho le tsa dopaminergic li ntse li le joalo. Litaba tsa dopamine, tyrosine hydroxylase le litekanyetso tsa anatomic tsa dopaminergic innervation ea frontal cortex e nyolohela tlhoro pejana feela ea bohlankana le ho oela ka har'a li-primates tse seng tsa motho (Goldman-Rakic le Brown 1982; Rosenberg le Lewis 1994; Rosenberg le Lewis 1995; Erickson et al. 1998). Likahare tsa dopamine tsa Striatal li eketseha ka nako ea bocha ho batho (Haycock et al. 2003) leha matšoao a mang a synaptic a kenyelletsa tyrosine hydroxylase, transporter ea vesicular (VMAT2) le transporter ea plasma membrane (DAT) qalong ea bocha.Meng et al. 1999; Haycock et al. 2003).
Le ha "mechine" eohle ea "methapo" ea phetisetso ea dopaminergic e fumaneha hang kamora ho hlaha, lintlha tse ngata tsa tšebetso ea dopaminergic li fetoha haholo nakong ea bohlankana. Lits'oants'o tse ngata li fihla liphatlalatsong tse phahameng ka ho fetesisa lilemong tsa bocha kapa ho ba motho ea moholo lilemong tse lateloang ke ho oela maemong a batho ba baholo. Liphetoho ho li-receptor tsa postynaptic li hlalositsoe ka botlalo. Overexpression ea D1 le D2 receptors pele ho nts'etsopele le kamora moo ea fokotseha nakong ea bocha ho tlalehiloe lithutong tse 'maloa (Meng et al. 1999; Seman 1999). Phuputso ea morao-rao ho batho e bonts'a tahlehelo e ts'oanang ea matšoao a bokhachane nakong ea bohlankana (Haycock et al. 2003).
Boemo ba mosebetsi oa Forebrain Dopaminergic in Rodents
Ho kenella hoa li-neuron tsa dopaminergic tse kenang bokantle ba litoeba ho tšoana hantle le ho tlalehiloeng ka holimo bakeng sa li-primates tsa batho bao eseng batho. Dopaminergic neurons eo qetellong e kenang kahare ea dorsal le ventral striatum le frontort cortex litekong tsa tsona li arola karolo ea ho qetela nakong ea bohare ba mpa (Lauder le Bloom 1974). Matšoao ohle a limolek'hule a dopaminergic neurons a hlahisoa maemong a bohlokoa pele a hlaha, empa kholo ea ho phatloha ha dopamine ho boloka phatla ea phatlo e hlaha kamora ho hlaha ho rat. Ho tloha PN5 ho isa ho PN40, matšoao a mangata a kenyelletsa dopamine, tyrosine hydroxylase, D1 le D2 receptors le dopamine transporter e eketseha haholo ho striatum, n. bokaholimo le kotloloho ea pele (Coyle le Axelrod 1972; Porcher le Heller 1972; Nomura et al. 1976; Kirksey le Slotkin 1979; Giorgi et al. 1987; Gelbard et al. 1989; Broaddus le Bennett 1990; Broaddus le Bennett 1990; Rao et al. 1991; Coulter et al. 1997; Tarazi et al. 1999). Ho phahama ho makatsang ha matšoao ana kaofela a dopaminergic ho etsahala libekeng tse peli ho isa ho tse tharo kamora ho hlaha, pele ho nako ea bocha, empa ho hola ha mmele ho tsoela pele ho fihlela bonyane PN60. Frontal cortex innervation in the rat lags hanyane ka morao ho libaka tse eketsehileng tsa caudal, hoo e batlang e le dopaminergic innervation tsohle e fihlang kamora nako le ho fihlella maemo a batho ba baholo ka PN60 (Kalsbeek et al. 1988).
Li-receptor tsa dopamine ka litoeba li nyoloha ka mor'a ho rongoa hoa bongoana joalo ka ha ho tlalehiloe bathong (Huttenlocher 1979; Giorgi et al. 1987; Gelbard et al. 1989; Teicher et al. 1995; Montague et al. 1999; Tarazi et al. 1999; Andersen et al. 2000; Tarazi le Baldessarini 2000; Andersen et al. 2002). Le ha e ntse e le lets'oao la matšoao a presynaptic ha lea ka la bonoa thutong e le 'ngoe e sebelisang lifensetere tse tšesaane (Tarazi et al. 1998), radioligand e sebelisitsoeng lithutong tsena (GBR12935) e hokahana ka tsela e fapaneng ho ea DAT ho feta WIN 35,428, radioligand e bonts'ang khokahano e ntlafatsang lipakeng tsa thibelo le tšitiso ea (Xu et al. 1995). Lithuto tsena li fana ka maikutlo a hore ho roka khokahano ea bohlokoa ho tloha ho khoesoa le ho ba motho e moholo ho ka bapala karolo phetohong ea boitšoaro.
Maemo a dopamine ea extracellular a tsamaellana le keketseho e tlalehiloeng ea letsoalo la batho ba bolokang mafu a hlahang lilemong tsa bocha. Maemo a dopamine ea basal extracellular joalo ka ha a lekantsoe ke voltammetry kapa microdialysis a tlase nakong ea bocha ho feta ho ba motho e moholo.Gazara et al. 1986; Stamford 1989; Andersen le Gazzara 1993; Laviola et al. 2001).
Ketsahalo ea Forebrain Dopaminergic Neurons nakong ea bocha
Tlhaloso e fetileng e fana ka maikutlo a hore dopaminergic innervation ea sepheo sa 'mele ea bokhachane e haelloa lilemong tsa bocha, e sebetsa ka botlalo nakong ea bohlankana, e lateloe ke "ho itšupa' ha liphoofolo e se e le batho ba baholo ka botlalo. Leha ho le joalo, mehato ea ts'ebetso ea neuron ea dopaminergic e fana ka maikutlo a hore li-neuron tsena li sebetsa haholo nakong ena ea nako. Lithuto tse sebetsang li bonts'a hore li-neuron tsa dopaminergic li fihlella boholo ba ts'ebetso nakong ea bohlankana, hoo e ka bang ka nako eo litlhoko tsa ts'ebetso ea ts'usumetso e khothalletsang. Dopaminergic neurons e fumana mekhoa ea ho thunya ea batho ba baholo e kenyeletsang ts'ebetso ea autoreceptor le mokhoa o phatlohileng oa ho thunya pejana feela kapa nakong ea bohlankana (Pitts et al. 1990; Tepper et al. 1990; Lin le Walters 1994; Wang le Pitts 1995; Marinelli et al. 2006; McCutcheon le Marinelli 2009). Boithuto ba Microdialysis le neurotransmitter li bontšitse hore li-axonal tranerals, gamma hydroxybutyrate, le li-psychomotor tse susumetsang li ka kenya tšebetsong dopaminergic neurons hantle pele li khoesoa (Erinoff le Heller 1978; Cheronis et al. 1979). Lithuto tse le 'ngoe tsa thuto ea lisele tsa dopamine li bonts'a hore tekanyo ea ho thunya e phahame haholo nakong ea bohlankana, mohlomong hobane e sa thijoe ke thibelo ea autoreceptor (Marinelli et al. 2006). Laborator ea rona e bonts'itse hore cocaine e susumetsang dopamine e ngatafala e kholo ho dorsal striatum ho bongoaneng ho feta likhoto tse kholo le ha ho lokolloa dopamine e ngata (e bonts'a mabenkele a bokuli) e fokola haholo (Walker le Kuhn 2008). Tekanyo ea moetlo oa phetoho ea tekanyo ea HVA / DA le eona e phahame haholo lilemong tsa bocha ho feta likhoto tse kholo Setšoantšo sa 1). Ho fumanoe liphumano tse tšoanang phuputsong e neng e bapisa 18, 30 le 110 li-rats tsa khale tsa letsatsi (Teicher et al. 1993). Lintlha tsena kaofela li fana ka maikutlo a hore li-neurop tsa dopaminergic tse projeke ea ho bonts'a liphofu tse amanang le ts'ebeliso ea lithethefatsi e kanna ea se be le maemo a batho ba baholo ba bolulo, empa haeba ho na le letho le arabelang ho kenyelletso ea neuronal.
Ts'ebetso e ntlafalitsoeng ea li-neuron tsa dopaminergic lilemong tsa bocha li ka 'na tsa se ke tsa fetela ho li-neuron tsa dopaminergic tse ka hare ho mokokotlo oa mokokotlo. Letoto le letle la boithuto lithutong tsa boko ba rat le bontšitse hore litakatso tsa mahlakore ka bobeli a D1 le D2 li ne li le sieo cortex nakong ea karolo e le ngoe ea ntlafatso e hlalositsoeng ka holimo (Tseng le O'Donnell 2005; Tseng le O'Donnell 2007). Leha ho le joalo, lithuto tsena li sebelisitse sistimi e fapaneng ea mohlala, 'me lintlha tsa pheletso tse tšoanang ha li so hlahlojoe ho dorsal kapa ventral striatum nakong ea bohlankana. Ho ka etsahala hore litlatsetso tsa cortical dopaminergic li ka holisa ka lebelo le fapaneng hanyane ho feta le kenyelletso ea striatal.
Karolo ea 3: Thobalano, Steroids ea Gonadal le Bokhoba ba Adgencence
Ho hlaha ha phapang ea thobalano ts'ebelisong ea lithethefatsi tse tlatsetsang ke batho
Phapang pakeng tsa thobalano ea tšebeliso ea lithethefatsi ke batho e hlaha nakong ea bohlankana. Le ha ho le joalo, litlamorao tsa ho ikatisa li susumetsoa ke ho fetola likarolo tsa basali le lintho tse ling tse susumetsang sephetho sena. Qaleho ea ts'ebeliso ea lithethefatsi e batla e lekana ho bashanyana le banana (Johnston et al. 2007; NHSDUH 2007). Baroetsana ba lilemong tsa bocha ba na le monyetla oa ho noa joala, ho tsuba matekoane le lithethefatsi tse ling tse seng molaong le ho sebelisa lithethefatsi tse ngata e le banna ba banyenyane ba lilemong tsa bocha.Johnston et al. 2007; NHSDUH 2007; Palmer et al. 2009). Tšebeliso ea koae, joala, matekoane le lithethefatsi tse ling tse seng molaong li eketseha ka mokhoa o ts'oanang nakong ea bocha ka tsela e ts'oanang ho banna le basali. Phapang e kholo e hlaha hamorao bongoaneng, ha ba batona ba le menyetla ea ho ba joala le basali hore ba tsube (Mocha et al. 2002; Cropsey et al. 2008). Boithuto bo bong bo kenyelletsang bacha ba seng ba holile bo bontša hore ts'ebeliso ea banna ea matekoane le lithethefatsi tse ling tse seng molaong li feta tsa basali (Terry-McElrath et al. 2008) Le ha li-cohorts li fapana ebile lithutong tse ling, ts'ebeliso ea lithethefatsi tse "thata" joalo ka heroin le cocaine li tšoana le ho banna le ba batšehali (Gerra et al. 2004). Ka kakaretso, liphapang tse peli tse kholo tsa thobalano tšebeliso ea lithethefatsi (tšebeliso ea lithethefatsi khafetsa ke banna le "telescoping" ea tsoelo-pele ho ts'ebeliso ea ts'ebeliso ea tlhekefetso ea basali) li hlahella qetellong ea bocha (Nolen-Hoeksema 2004; Ridenour et al. 2006).
Ho kena bohlankaneng e le tšusumetso ea ho ba tlokotsing ea ho lemalla bokhobeng.
Ho kena bohlankaneng e le Karolo e Ntle ea Kholiso ea Boko ba Bacha
Ho kena bohlankaneng ho ba le tšibollo e kholo 'me ho etsa hore boko ba bongoaneng bo hōle. Mefuta ea liphoofolo e lumellane haholo le lithuto ho batho, hoo ho tla buisanoa ka karolo ena. Ho batho, nts'etsopele ea "pubertal" e etsahala ho feta lilemo tse fapaneng ho latela semelo sa morabe, setso le bophelo bo botle ba motho ka mong, empa lefats'eng le tsoetseng pele, banana ka kakaretso ba fumana maemo a baholo ba estradiol le progesterone ka lilemo 14-15 (ha ba ea matsatsing) le bashanyana. fumana maemo a batho ba baholo ba testosterone selemo hamorao, ka lilemo tsa 16-17 (Styne le Grumbach 2008). Ka mokhoa o ts'oanang, ka litoeba, basali ba na le li-hormone tsa "cyclic gonadal" tsa batho ba baholo ka letsatsi la ho beleha ha PN35 ha ba e-ba le estrus ea bona ea pele, athe banna ba bona ho eketseha ha testosterone ho tloha PN25 ho fihlela PN60. Lekhetlong lena, ho kena bonneng kapa bosaling ho felletseng ka bong bohle 'me liphoofolo li holile ka botsona (Lee et al. 1975; Korenbrot et al. 1977; Ojeda et al. 1980; Ojeda et al. 1986).
Ka bobeli litla-morao tsa li-activation le tlhophiso ea li-steroid tsa gonadal li kenya letsoho haholo phetohong ea sebopeho sa boko le tšebetso nakong ea ho kena bohlankaneng. Nakong ea bokhachane, banna le basali ba fihlella maemo a batho ba baholo ba li-hormone tsa ho ba le bana, tseo ka nako eo li laolang litebello tsa bona khafetsa: ts'ebetso ena e fana ka litlamorao tsa li-steroid tsa gonadal tse laolang tšebetso ea boko ka mokhoa o tsoelang pele le o fetohelang. Leha ho le joalo, ho na le kananelo e ntseng e eketseha ea hore ho nyoloha ha li-steroid tsa gonadal nakong ea ho kena bohlankaneng ho ba batona le ba batšehali ho kenya letsoho phethehong ea karohano ea botona le botšehali ka ho baka lits'ebetso tse ke keng tsa fetoloa - litlamorao tsa mokhatlo.Cooke et al. 1998; Becker et al. 2005; Schulz et al. 2009).
Litšoantšo tse amanang le botona le botšehali ka sebopeho sa boko tse hlahang nakong ea ho kena bohlankaneng le tsona li susumetsoa ke gonadal steroids. Ha e le hantle, sebopeho sa boko ba motho bo hlasimoloha ka thobalano esita leha o hlahaGilmore et al. 2007) le khatello ea kholo ea phetoho sebopeho sa boko ho pholletsa le boroetsana e fapana ho banana le bashanyana hantle pele ba kena bohlankaneng. Banana ba fihla sehlohlolong sa taba ea bohlooho xNUMX-1 lilemo pele ho bashanyana (Giedd et al. 2006). Boitšoaro bona bo susumetsoa hape ke sethala sa lipapatso (De Bellis et al. 2001). Liphetoho metsong e meng ea boko ho kenyeletsa amygdala le hippocampus li bonts'a sethala sa ntlafatso ea "pubertal" le liphetoho tsa taba ea bohlooho li itšetleha ka ho potoloha ha estradiol ho banana le testosterone ho bashanyana (Peper et al. 2009). Mekhabiso ea botona le botšehali e sebopeho sa boko mefuteng e hlalositsoe hantle mme e feta hole le tlhahlobo ea hona joale. Maikutlo a mangata a matle (MacLusky le Naftolin 1981; Cooke et al. 1998; Morris et al. 2004; Ahmed et al. 2008).
Ho kena lilemong tsa bocha le ho fetoha ha boitšoaro nakong ea bocha
Ho eketseha ha sekhahla sa lihormone tsa gonadal nakong ea bokhachane ho tlatsetsa mofuteng oa boits'oaro le sebopeho sa boko le tšebetso. Ho basali, ho eketseha ha li-pubral ho estradiol ka bobeli le progesterone hoa hlokahala bakeng sa ponahalo ea tlatsetso e felletseng ea boits'oaro ba basali le ho banna, testosterone le estradiol e hlahisitsoeng ho tloha ho aromatization ea testosterone e kenya letsoho litlamorao tsa ts'ebetso le tlhophiso. Litlhahlobo tse 'maloa tsa morao-rao mabapi le hore na li-steroid tsa gonadal li kenya letsoho joang ho nts'etsopele ea ts'ebetso ea ho ikatisa le boits'oaro ba thobalano nakong ea bongoaneng e phatlalalitsoe (Romeo et al. 2002; Romeo 2003; Sisk et al. 2003; Sisk le Zehr 2005; Schulz le Sisk 2006). Li-testicular le li-ovarianids li lumella ho qaleha ha thobalano - boitshwaro bo nepahetseng ba setjhaba, ho ba mabifi le boits'oaro ba motsoali hammoho le boits'oaro ba ho ba le bana. Ha boholo ba data bona bo bokelitsoe litoeba, likhoto le li-hamsters, ho fumanoe lipatlisiso tse tšoanang ho batho ba nang le boiphihlelo ba ho kena bohlankaneng (bo hlahlobe ho (Sisk le Zehr 2005).
Phapang pakeng tsa batho ba bong bo fapaneng le ba boitšoaro e amanang le tšebeliso ea lithethefatsi le eona e hlaha nakong ea bongoaneng (Windle et al. 2008). Ho batla ho bontšoa ka litheko tse phahameng haholo hangata ho amanang le tlhekefetso ea lithethefatsi ho banna ho feta basali (Butkovic le Bratko 2003; Nolen-Hoeksema 2004). Ho batla ho sesa ho phahame haholo nakong ea bokhachane kapa boroetsaneng ho bashanyana le banana ha ba bapisoa le bana ba lilemo tse tšoanang sethaleng sa pejana (Quevedo et al. 2009). Ho feta moo, boemo ba lihormone tsa pubertal bo kenya letsoho liketsahalong tsena. Testosterone e kopantsoe hantle le ho batla maikutlo ho banna ba baholo ka bobeli (Coccaro et al. 2007le banna ba lilemong tsa bocha (Martin et al. 2004) ha estradiol e phahameng e kopantsoe le maemo a tlase a takatso ea maikutlo (Balada et al. 1993) leha liphetoho tsa pubertal li sa tlaleheloa. Kamora nako, litekanyetso tsa testosterone nakong ea ho kena bohlankaneng li tsamaellana ka mokhoa o nepahetseng le takatso ea maikutlo le tšebeliso ea lithethefatsi tse tšoanang (Martin et al. 2002) Le ha ho na le monyetla oa hore liketsahalo tsa lihormone ho banna le ba batšehali li kenya letsoho ho hlaha ha phapang ea botona le botšehali litloaelong tse matla tsa tlhekefetso, boithuto ba lipapatso tsa pubertal liketsahalong tsena tsa bohlokoa tsa ntšetso-pele e sa le bohlankana.
Ho hlaha ha phapang ea thobalano ketsong ea lithethefatsi tse tlatsetsang
Ts'usumetso e tsitsitseng ea ts'ebetso ea dopaminergic ke estradiol e hlahlojoang ka holimo e bontša ho phahama ha estradiol e etsahalang ka ho qala ha estrous cyclicity ho lokela ho baka keketseho ea tokollo ea dopamine le karabong ea boitšoaro ho lithethefatsi tse lemalloang. Ebile, phapang ea thobalano mekhoeng e mengata e amanang le bokhoba ba tahi e hlahella nakong ea bocha litenteng, le lithutong tse nyane haholo tse teng. Leha ho le joalo, bopaki bo hlahang bo bontša hore li-steroid tsa ovari le tsa testicular li ka kenya letsoho liphetoho tsena.
Laboratori ea rona e bonts'itse hore likhoto tsa banna ba lilemong tsa bocha ba bonts'itse ts'ebetso ea cococaine e matlafalitsoeng, ts'ebetso e kholo ea lits'ebetso tse tšoaeang methapo ka har'a dorsal striatum (joalo ka ha e lekantsoe ke ts'ebetso ea c-fos), le tlhotlheletso e kholo ea tekanyetso e le 'ngoe ea boitšoaro ba locomotor ho feta motho e moholo.Caster et al. 2005; Caster et al. 2007). Papiso ea koae e tsosang takatso ea koae ho batho ba lilemong tsa bocha le ba batona le ba batšehali e bontšitse hore bacha ba batona le ba batšehali ba arabela ka mokhoa o ts'oanang le cocaine, le hore phapang ea thobalano e mabapi le boitšisinyo ba koae e hlaha nakong ea bohlankana. Phapang ea botona le botšehali e bonts'a ho fokotseha hoa ts'ebetso e matlafatsoang ke koae le banna le keketseho ea pherekano e susumetsoang ke koae ho ba batšehali (Parylak et al. 2008). Phetoho e ts'oanang ea ntlafatso ea karabelo ea locomotor ho methylphenidate e tlalehiloe: athe bacha ba batona le ba batšehali ba bonts'a mokhoa o ts'oanang oa ho ts'oaroa ha methapo ea methapo, methylphenidate e hlohlelletsa haholo ts'ebetso ea locomotor ho basali ba baholo ho feta ho ba batona (Wooters et al. 2006). Ho hlohlelletsoa hoa morphine ho ile ha bonts'a mokhoa o fapaneng: ba batona ba lilemong tsa bocha ba bontšitse tšusumetso e kholo ho feta banna ba baholo, empa batho ba lilemong tsa bocha le ba baholo ba ne ba lekana le banna ba baholo - ho ne ho na le phapang ea botona le botšehali nakong ea bocha empa eseng motho e moholo.White et al. 2008). Boikutlo bo boholo ba litoeba tse tona ho thibela thunya ka nicotine e amanang le botšehali bo hlaha kamora ho ba lilemong tsa bocha (Lopez et al. 2003) Qetellong, ts'oaro ea locomotor e amanang le tekanyetso e tlase ea ethanol e eketseha ha litšoene tsa lilemong tsa bocha li ba batho ba baholo (Schwandt et al. 2007).
Liphapang tsa botona le botšehali tsa maikutlo le tsona lia hlaha lilemong tsa bocha. Tšusumetso ea maikutlo lipakeng tsa nicotine le psychostimulants cocaine le amphetamine li kholo ho banna ho feta likhoto tsa bocha tsa basali (Collins le Izenwasser 2004; Collins et al. 2004). Phapang pakeng tsa botona le botšehali ka kutloisiso ea ethanol ho litoeba le eona e tlalehiloe ho batho ba baholo empa eseng litoeba tsa bocha, ho fana ka maikutlo a hore liphapang tsena li hlaha nakong ea bongoaneng (Itzhak le Anderson 2008). Boikutlo ba moea ba tlhotlheletso ea sethoathoa ka basali empa e se banna bao eseng banna bo tlalehiloe lilemong tsa bocha.Schwandt et al. 2008).
Phapang pakeng tsa botona le botšehali ho litlamorao tse matlafatsang tsa lithethefatsi tse lemalloang le tsona lia hlaha lilemong tsa bocha. Boikutlo bo boholo ba basali ho cocaine CPP bo hlaha nakong ea bocha (Zakharova et al. 2009). Limpimpi tse tšehali empa ha li lilemong tsa bocha li na le CPP e kholo ho cocaine ho feta banna ba baholo.Balda et al. 2009). Phuputso e 'ngoe e tlalehiloe hore ha ho phapang pakeng tsa thobalano ho morphine kapa cocaine CPP ha ho bapisoa le likhoto tsa lilemong tsa bocha, empa palo ea lithuto tse lekiloeng e ne e le nyane haholo hore ho ne ho ka se be bonolo ho bona phapang e joalo ntle le haeba e ne e le kholo haholo (Campbell et al. 2000).
Liphapang tsa botona le botšehali tsa ho itaola lithethefatsi tse ngata tse lemalloang li hlaha nakong ea bohlankana. Re bontšitse hore likhoto tsa basali tse seng li le baholo empa eseng pele ho nako li sebelisa cocaine e ngata 'me li-laboratri tse peli li tlalehiloe ka ponahalo ea ho iphumanela ka potlako ea koae nakong ea bohlankana (Perry et al. 2007; Carroll et al. 2008; Lynch 2008; Walker et al. 2009). Le ha likhoto tsa banna le tsa basali tse lilemong tsa bocha li ba le taolo ea nicotine ka potlako ho feta batho ba baholo, maemo a boits'oaro a hlile a theohela ho banna ha ba kena lilemong tsa ho ba batho ba baholo, ha ba batšehali ba boloka maemo a ho ja haholo (Levin et al. 2003; Levin et al. 2007). Basali le ba batšehali ba bontša mokhoa o tšoanang oa taolo ea ho ikatisa tlasa bohlankana empa bofelong ba bocha, basali ba nka nicotine e fetang ea ba batona (Lynch 2009). Kamora nako, litoeba tsa bocha li ipehetse litekanyetso tse fokolang tsa oxycodone ho feta batho ba baholo, empa sephetho sena se ile sa hlalosoa e le kutloisiso e kholo ho litlamorao tsa oxycodone ho dopaminergic neurotransmitter hobane li bonts'itse keketseho e fetelletseng ea dopamine ho "ventral striatum" qetellong ea boitaolo.Zhang et al. 2009).
Ho hlaha hoa phapang ea ho ts'oaroana hoa thobalano le ho joala joala ka mefuta eohle le litabeng tsa batho bao eseng batho, leha ho le joalo, liphapang tse fapaneng tsa thobalano li its'etleha ka mefuta. Likhoto tsa basali li noella joala ho feta likhoto tsa banna, 'me phapang ena ea thobalano e hlaha nakong ea bocha.Lancaster le Spiegel 1992; Lancaster le ba bang. 1996). Boithuto bo le bong bo teng bo bonts'a hore ba batona le ba batšehali ba kentse li-ethanol tse lekanang lithutong tsena (Schwandt et al. 2008).
Liphetoho tsa nts'etsopele ea likarabo ho amphetamine li fapana le lithethefatsi tse ling tse ithutileng mme kahoo tsena li hlalosoa ka thoko. Bobeli ba batona le ba batona ba lilemong tsa bocha ba iphumanetse ho potlakela ho feta ba baholo thutong ea Shabazi (Shahbazi et al. 2008). Ba batona ba lilemong tsa bocha ba ithutile ho feta ha basali ba baholo, athe basali ba baholo ba ne ba feta basali ba baholo lilemong. Phuputsong e 'ngoe, basali ba lilemong tsa bocha ba bontšitse maikutlo a matla ho feta amphetamine ho feta basali ba baholo kapa ba batona ba lilemo life kapa life, empa ha ho liphapang tse ileng tsa bonoa ho tsa thobalano ka har'a pherekano kapa moferefere oa CPP phuputsong ena, e khelohang lingoliloeng.Mathews le McCormick 2007). Lebaka le leng la bohlokoa la ho toloka liphapang tsa thobalano ho amphetamine self-management ke hore amphetamine metabolism e ntlafatsoa ke testosterone, 'me ka hona e ka fetoha liphetoho nakong ea bocha.Meyer le Lytle 1978; Becker et al. 1982; Media-Halle et al. 2005).
Ho na le likheo tse teng tsebong ea rona mabapi le phapang ea thobalano litlamorao tsa lithethefatsi tse lemalloang liphoofolong tsa bocha. Ha ho na leseli le fokolang ka litlamorao tse matlafatsang tsa cannabinoids. Higuera-Matas o ile a etsa lipatlisiso ka litlamorao tsa batho ba baholo ba ho phekola likhoto tsa banna le tsa basali ka "X1 agonist CP55,940" ea PN28-38 mme a supa hore basali ba bonts'a ntlafatso ea boikoetliso ba koae.Higuera-Matas et al. 2008; Higuera-Matas et al. 2009). Wiley le basebetsi-'moho ba bapisitse litlamorao tse bohloko tsa THC ho cannabinoid tetrad: ea catalepsy, hypolocomotion, analgesia le hypothermia hammoho le mamello le sensitization e latelang THC. Ba fumane hore bacha ba basali ba ne ba sa ts'oenyehe ho feta batho ba baholo ba basali ho isa catalepsy, antinociception le hypothermia mme ba rata ho mamella haholo, athe ba batona ba lilemong tsa bocha ba ne ba amehile haholo ka tšitiso ea pherekano ho feta banna ba baholo.Wiley et al. 2007). Habohlokoa ka ho fetisisa, ha ho na lipatlisiso tsa liphetoho liketsong tsa lithethefatsi tse lemalloang lilemong tsa bocha litheong tsa batho bao e seng batho ntle le tse peli tse tlalehiloeng ethanol.
Karolo ea Gonadal Steroid Karolong ea Phallo ea Phapang Litabeng tsa Thobalano ka Liphello tsa Lithethefatsi tse Tlatsehang ho Ada.
Boithuto ba phapano ea thobalano ea boimana le boits'oaro bo sa tsitsitseng bo bonts'itse hore ho kena bohlankaneng ho emela "nako e mahlonoko" eo ho eona litlamorao tsa mekhatlo ea lihlahisoa tsa li-gonadal li hlahisang litlamorao tse sa fetoheng mabapi le sebopeho sa boko le ts'ebetso ea botona le botšehali. Litlamorao tsa ts'ebetso ea li-steroid tsa gonadal le tsona li qala nakong ea ho kena bohlankaneng, ka hona lits'ebetso tsena ka bobeli li ka kenya letsoho ho hlaha ha litsoantso tsa botona le botšehali ho ba kotsing ea ho lemalla nakong ea bohlankana. Lithuto tsena li bonts'a hore fensetere ea pele-pele ea pelehe le kamora ho hlaha e kenya letsoho litlamorao tsa mokhatlo tse sebelisang lithethefatsi tse lemalloang.
Lithuto tsa boits'oaro li ts'ehetsa karolo ea li-steroid tsa mae a bomme le testicular phapusing ea thobalano ea boitšoaro mabapi le lithethefatsi tse tlatsetsang, empa ts'ebetso e amanang le litlamorao tsa mokhatlo le ts'ebetso ha e hlakileng. Lithuto tse 'maloa li ts'ehetsa karolo ea litlamorao tsa mokhatlo o hlophisitsoeng oa li-gonadal steroid liphellong tsa lithethefatsi tse lemalloang. Ovariectomy kapa masculinization ea malinyane a basali a basali ka kalafo ea androgen hang ka mor'a tsoalo e ile ea thibela ponahalo ea likarabo tse ntlafalitsoeng tsa basali ho litlamorao tse matlafatsang tsa amphetamine (Tšoarela le Stewart 1993; Tšoarela le Stewart 1994). Phuputso e le 'ngoe ea "estrogen bisphenol" e fokolang ea "estrogen" e bonts'a hore na ho pepesetsoa boitšisinyo ho ka susumetsa ho kenella ha dopaminergic neurons, joalo ka ha ho pepesetsoa ha li-bacphenol matsatsing a prenatal 11-18 e hatelletse CPP -phetho e hlahisang mofuta oa CPP ho bana ba basali (Laviola et al. 2005).
Boithuto ba morao-rao bo tsoang laboratoring ea rona bo fana ka maikutlo a hore ho kena bohlankaneng ho ka emela fensetere e eketsehileng nakong eo litlamorao tsa li-steroid tsa gonadal li susumetsang litlamorao tsa lithethefatsi tse lemalloang. Letotong la lithuto re bapisitse litlamorao tsa ovariectomy ea pele ho nako le ea post-pubertal. Ovariectomy ebang e le motho ea moholo kapa pele a kena bohlankaneng kapa boroetsaneng e ne e hatella taba ea cocaine e matlafalitsoeng. Leha ho le joalo, pele ho nako, empa ho sa tsamaisoe ka sepheo sa tlhahiso ea "cocaine" e matlafalitse banna haholo (Kuhn le al. 2001; Walker et al. 2001; Parylak et al. 2008). Ho buoa pele ho nako ho entsoe ka PN25, kamora nako e tebileng e hlalositsoeng ea phello ea kutlo ea litlamorao tsa li-steroid ho mokhatlo o hlophisitsoeng oa boko. Lintlha tsena ka bobeli li tšehelitse karolo ea lihormone tsa mahe a botšehali ho basali, empa li boetse li fana ka maikutlo a hore tšusumetso e hlophisitsoeng ea androgen e neng e sa lemohuoe e kentse letsoho ho hola ho tloaelehileng hoa boitšoaro bo susumetsoang ke cocaine ho banna. Liphumano tsena li fana ka maikutlo a hore boitšoaro bo amanang le bokhoba ba gonadal steroid bo eketsa ho ba basali le ho ba hatella ho banna nakong ea bohlankana.
Ho hlaha ha phapang ea thobalano mosebetsing oa Dopaminergic nakong ea bocha
Boithuto bo shebiloeng ka holimo bo bonts'a hore ts'ebetso ea ts'ebetso ea methapo, matlafatso a amanang le lithethefatsi le taolo ea lithethefatsi e fetoha mekhabiso ea thobalano litenteng nakong ea bohlankana. Ha ho fanoa ka bohlokoa bo bonts'itsoeng ba ts'usumetso e khothalletsoang ke lithethefatsi ea li-neuron tsa dopaminergic ka phapang ena ea thobalano, hoa utloahala ho fana ka maikutlo a hore phapang ea thobalano ea mosebetsi oa dopaminergic e lumellana le litlamorao.
Phapang pakeng tsa thobalano ho anatomy ea dopaminergic monahanong ea bokong bo hlaha e le litonong. Ovtsharoff (Ovtscharoff et al. 1992) e bonts'a hore basali ba na le letsoalo le phahameng la dopaminergic fiber innervation ho caudate prenatally. Ho boetse ho fanoe ka maikutlo a hore botona le botšehali ho fapana le ho potoloha ha li-hormone ho ama li-neurop tsa dopaminergic bokong ba basali ba litoeba (Beyer le al. 1991; Kolbinger et al. 1991). Pontšo ea hore mokhoa oa testis o khethollang liphatsa tsa lefutso e hlahisoa ho li-neuron tsa dopaminergic moo e ka laolang polelo ea tyrosine hydroxylase e ikemetseng ea li-hormone tse eketsehileng ho ts'ehetsa monyetla oa hore molao o ikhethang oa thobalano oa li-neuron tsa dopaminergic o teng (Ho roka et al. 2006), leha sena e le sebaka se hlahang se nang le data e nyane.
Ho sa na le bopaki bo fokolang mabapi le phello ea li-steroid tsa gonadal tšebetsong ea dopaminergic nakong ea linako tse mahlonoko nakong ea peleho ea pelehi le kemelo ea pelehi. Leha ho le joalo, tlhaiso-leseling ea boits'oaro e fana ka maikutlo a hore ho pepesetsoa hoa banna ho androgen ka boeona kapa nakong ea bokhachane le ho pepesetsoa ha basali ho estrogen nakong ea bokhachane ho fana ka litekanyetso tsa bohlokoa tsa lihormone (bona tlhahlobo ea moraorao ea Becker (Becker 2009)). Boithuto bo bong bo seng bo ntse bo le teng ke bopaki ba hore li-steroid tsa gonadal ha li kenye letsoho khokahanong ea bongoana ea li-receptors tsa D2 (Andersen et al. 2002).
Tlatsetso ea Gonadal Steroid ho Liphetoho mosebetsing oa Dopaminergic nakong ea bocha
Laboratori ea rona e se e qalile ho tšoaea ho hlaha ha phapang ea thobalano libakeng tsa lisele tsa dopaminergic sebakeng sa substantia nigra le sebakeng sa karohano ea methapo le lipakanyo tsa bona tsa lefu bakeng sa ho utloisisa tlatsetso e ka bang teng ea ts'ebetso ea dopaminergic ho fetoleng menyetla ea ho lemalla nakong ea bongoana. Seo re se fumaneng nakong e fetileng se bonts'itse hore koae e ntlafalitsoeng ke dopamine ka har'a dorsal striatum e phahame haholo ho 3 bongoaneng ho feta likholong tsa banna ba baholo. Phapang ena ea nts'etsopele e ikhethile ho ea ka libaka, kaha ha e hlahe botebong ba liqhubu tsa nucleus (Walker le Kuhn 2008). Boithuto ba rona ba boits'oaro bo boletse esale pele hore ho qala ha estrous cyclicity ho basali nakong ea bocha ho ka thibela ho theoha ho ts'oanang ha tsoekere ho dopamine e matlafalitsoeng ke koae.
Ho etsa lipatlisiso ka monyetla ona, re ile ra lekanya ho ata ha dopamine ka linako tse fapaneng kamora taolo ea koae (10 mg / kg) bongoaneng (ka letsatsi 28) le motho e moholo (letsatsi la 65) likhoto tsa banna le tsa basali tse sebelisang ka potlako li-cyclic voltammetry joalokaha ho hlalositsoe pele ho bacha ka bobeli le batho ba baholo (Walker et al. 2000; Walker et al. 2006; Walker le Kuhn 2008). Setšoantšo sa 2 e bontša keketseho ea karolo ea dopamine e amanang le thothomelo ea motheo ho 20 Hz. Khokahano ea dopamine e matlafalitsoeng ke cocoaine e ne e le kholo haholo litekatsong tsa botona le botšehali ho bapisoa le batho ba baholo, mme ba batona le ba batšehali ba ne ba bapisoa. Le ha dopamine e matlafalitsoe ke koae e ne e le kholo ho feta ho batho ba batona le ba batšehali, ho theoha ho tloha bocheng ho ea ho motho e moholo ho basali ho ne ho fokola ho feta ho bonoang ho ba batona (Walker et al. 2000; Walker et al. 2006). Liphumano tsena li bontša hore ts'ebetso ea dopaminergic e oela nakong ea bocha ka tsela e ikhethileng ea thobalano. Leha ho le joalo, thuto ena e ne e sa khone ho khetholla tlatsetso ea mokhatlo kapa ts'ebetso ea ts'ebetso ea li-gonadal steroids ho liphetoho tsena ho lokolloe ha dopamine.
Lingoliloeng tsa batho ba baholo li bontša hore litlamorao tsa estradiol ke tšusumetso ea mantlha ea gonadal steroid ts'ebetsong ea dopaminergic ho likhoto tsa batho ba baholo. Leha ho le joalo, ya rona ya boitshwaroParylak et al. 2008) e bonts'itse hore litlamorao tsa bohlokoa tsa mokhatlo oa li-ovari kapa testicular steroid li ka kenya letsoho phetohong ea bocha mosebetsing oa endocrine. Ho etsa lipatlisiso ka monyetla ona, re tsamaisitse prepubertal castration kapa ovariectomy ho PN25, mme ra lekola dopamine ea cocaine e hlohlellelitsoeng matsatsi a 30 hamorao, ho ts'oana le lithuto tsa rona tsa boitsoaro bo fetileng. Liphetho tsa liteko tsena li bonts'itsoe Litšoantšo 3 'me and4.4. Joalokaha ho ka lebelloa, ovariectomy ea preubertal e ile ea fokotseha ka bongata ba koae (e hlahisang koae)Setšoantšo sa 3). Ho makatsang ke hore, ho tsamaisoa pele ho pele ho ile ha baka keketseho e kholo ea koae e khothalletsoang ke koae (e tsoekere).Setšoantšo sa 4). Ha ho fanoa ka litlamorao tse hlalositsoeng hantle tsa estradiol mabapi le ts'ebetso ea dopaminergic, ho thata ho khetholla monehelo o lekanyelitsoeng oa ts'ebetso ea ts'ebetso le tlhophiso liphellong tsa basali. Leha ho le joalo, boima ba lingoliloeng bo bonts'a ho haella ha litlamorao tsa androgen ho dorsal striatal dopamine e lokolloang liphoofolong tsa batho ba baholo e fana ka maikutlo a hore androgen e ka ba le tšusumetso e neng e sa hlophisoa mokhatlong o hlophisitsoeng mesebetsing ea dopaminergic nakong ea bongoaneng. Sephetho sena se tsamaisana le liphumano tsa boitshwaro tseo re li hlalositseng kaholimo, tse bonts'itseng kholiseho e kholo ea boitšoaro bo matlafalitsoeng ba koae ka mor'a ho lahla batho ba baholo empa e se batho ba baholo.
Mekhoa eo li-steroid tsa ovari le testicular li susumetsang tšebetso ea dopaminergic ho fihlela nakong ea bocha ha e tsejoe. Kaha re sa tsoa supa hore estradiol augments dopaminergic likarabo ho karolo ea eona ka ho boloka nomoro ea dopaminergic neuron, re ile ra etsa phuputso ea sefofane ho bona hore na ho fapana ha thobalano ho palo ea dopaminergic neuron ho hlahile nakong ea bongoaneng. Ho etsa lipatlisiso ka monyetla ona, re bolaile likhoto tsa banna le basali ho PN21, 28, 42 le 65 mme re balile nomoro ea dopaminergic neuron sebakeng sa substantia nigra le ventral tegmental, nuclei ho tloha moo likhakanyo tsa dopamine ho ea bokong, re sebelisa stereology e sa ts'oaneng. .
Liphoofolo li entsoe ka mokhoa o sa tsotelleng 'me li entsoe ka mokhoa o phollatsi ka 10% e sa jeleng paate. Kamora ho tlosoa, litlolo li ile tsa ntšoa 'me tsa beoa ka mora bosiu ho 10% formalin, tsa lekanyetsoa tharollo ea 30% sucrose cryoprotectant' me ea bolokoa ho 4 ° C. Likarolo tsa "coronal serial" (30 μm) li ne li khaoloa ka sekepeng, li kenngoa ka har'a li-slide ebe li oma bosiu bo le bong ho 37 ° C. Likarolo li ile tsa thuloa ka har'a PBS 'me tsa kenngoa ka har'a 0.3% hydrogen peroxide-methanol bakeng sa metsotso ea 30, e tsitsitsoe' me e koetsoe ka 0.5% BSA + 0.3% Triton X-100 bakeng sa metsotso ea 15. Kamora ho thibela, likarolo li ile tsa kenngoa ka har'a antibody ea mantlha e kentsoeng ho thibela buffer (1: 10000, Immunostar, Inc., Hudson, WI) bosiu ho 4 ° C. Letsatsing le hlahlamang, likarolo li ile tsa phuthoa tsa ba tsa kenngoa kahare ho anti-mouse yesibini antibody (1: 1000, Vector Labs, Burlingame, CA) bakeng sa hora ea 1 ka mocheso oa kamore. Likarolo li ile tsa phuthoa tsa ba tsa kenngoa ka har'a avidin-biotin bakeng sa hora ea 1 mochesong oa kamore, e hlotsoe le ho ts'oaroa ka DAB (Vector Labs). Likarolo li ne li hahuoa, li ntšoa metsi ka ho sebelisa li-alcohols tse halikiloeng, 'me li kentsoe ka cresyl violet, li kenngoa' me li koaheloa. Tekanyo e sa laoleheng ea litekanyetso tsa palo eohle ea 'mele ea lisele tsa TH-IR le TH-IN ho SNpc le VTA e ile ea etsoa ho sebelisoa mokhoa oa ho bona likarolo (West et al. 1991). Sistimi ea ho bala ea k'homphieutha e nang le microscope ea Nikon Optiphot-2, kh'amera (Dage) le sethala sa makoloi (Ludl) li sebelisitsoe ho hakanyetsa palo e felletseng ea lisele. Litopo tsa motho ka mong li ne li bonoa ka lense ea qoeliso ea oli ea 100 × (lipalo tsa ho omisa = 1.3). Ho ile ha baloa lisele tse lekaneng ho fihlela phoso e felletseng e neng e le ≤ 0.10. Boithuto bona bo ile ba etsoa ntle le ho khutlisetsa mocheso ka hare ho antigen, 'me linomoro tsa sele li ne li le tlase ho feta kamoo ho ka fumanoang ka mokhoa ona oa morao. Leha ho le joalo, mokhoa o hlakileng le o sa lebelloang o hlahile tlhahlobong ena. Joalokaha ho bontšitsoe Setšoantšo sa 5, ho oa ho hoholo ha linomoro tsa sele ea DA ho etsahetse lilemong tsa bocha. Ho oa hona ho ne ho bonahala e le sebaka sa basali naheng ea 65, ha phapang ea botona le botšehali e hlaha.
Liphumano tsena li fana ka maikutlo a hore leqhubu le leholo la lefu la lisele tsa dopaminergic le etsahala nakong ea bocha ho likhoto, ho banna le ho basali. Maqhubu a mabeli a pele a lefu la selefouno ea apoptotic a hlaha hang kamora ho hlaha le ka PN14 (Jackson-Lewis et al. 2000; Burke 2003; Burke 2004). Kameho ea ho oa nakong ea bohlankana ho ts'ebetso ea dopaminergic ha e hlake, hobane ho etsahala ka nako e ts'oanang moo letsoalo la ba sa bolokang libakeng tsa phetheho le ntseng le eketseha (bona kaholimo). Ho 'nile ha fanoa ka maikutlo a hore lisele tse tlisoang ke apoptosis ke tsona tse sa fihlelleng sepheo sa tsona ka nepo' me ha li a ka tsa fumana tlhahiso ea trophic ho tsoa ho li-neurons tsa sepheoOo et al. 2003; Burke 2004). Ho hlaha ha phapang ea thobalano palo ea li-dopamine neurons kamora ho kena bohlankaneng kapa boroetsaneng ho ts'ehetsa mohopolo oa rona oa mantlha oa hore litlamorao tsa trophic tsa estradiol li ka kenya letsoho ho hlokomeleng li-neuron tsa dopaminergic bophelong ba batho ba baholo. Hoa makatsa hore liphetoho lipalo tsa li-neuron tsa dopaminergic li bapisa le liphetoho liphellong tsa cocaine mabapi le tokollo ea dopamine eo re e boneng: phokotso e kholo nakong ea bocha, karolo eo e neng e le ea thobalano feela. Hajoale re ntse re etsa lipatlisiso hore na liphetoho tsa anatomic 'meleng oa sele le / kapa libakeng tsa maqhubu li kenya letsoho taolong ea gonadal steroid ea boits'oaro bo amanang le lithethefatsi.
Bohlokoa ba Liphetoho tsa Bocha Boemong ba Mosebetsi oa Dopaminergic oa Forebrain
Lithuto tse hlahlojoang ka holimo li bonts'a hore ts'ebetso ea dopaminergic ka har'a dorsal striatum e fetoha setopo sa ho qetela se lateloang ke "ho khutlela morao" ts'ebetsong ea batho ba baholo ha bacha ba ntse ba hola. Phapang pakeng tsa thoabalano mosebetsing oa dopaminergic le boits'oarong bo laoloang ke dopamine li hlaha nakong ena ea nako. Litlamorao tsena li bonahala li bonts'a ho qala hoa ts'ebetso ea estradiol ho ea mosebetsing oa dopaminergic ho basali mme mohlomong le phello ea mokhatlo ea androgen e hatellang tšebetso ea dopaminergic ho ba batona. Setšoantšo sa 6 e akaretsa morero o le mong o ka hlalosang liphetho tsa hona joale. Ho tloha ka letsohong le letšehali ho ea ho le letona, palo e bonts'a mekhahlelo e meraro ea nts'etsopele ea neuron ea dopaminergic. Phanele ea ka ho le letšehali e bontša dopamine neurogeneis. Sethala sa bohareng se supa nako ea ts'ebetso ea axon le ho bolokoa ha liphofu tse etsahalang nakong ea bophelo ba ka mor'a ho ba le bohlankana kapa boroetsana. Karolo ea ho qetela ea nts'etsopele ea dopaminergic neuron e bonts'oa papaling e nepahetseng, ha li-receptors li "prune" khutlela. Li-neurone tsa Dopaminergic li lahleha mohato o mong le o mong oa ts'ebetso, ho ipapisitse le data thutong ea hona joale le e phatlalalitsoeng pele (Burke 2003; Burke 2004). Re kholoa hore nakong ea bocha, karolo ea ho qetela ea lefu la lisele tse tsoang ho dopaminergic ka hara mpa e mpefatsoa ke androgen mme ea emisoa ke litla-morao tsa tropic tsa estradiol. Sena se bontšoa ke lisele tse fokolang tse bohareng le ba le letona bakeng sa banna, le "neuron" e putsoa ka tlase e bonts'a palo ea li-neuron tse bolokiloeng ke estradiol ho basali. Neuron e putsoa e boetse e kenyellelitsoe karolong e ka letsohong le letšehali, hobane lithuto tsa setso li bontšitse hore basali ba ka ba le li-neuron tse eketsehileng maemong a pele a nts'etsopele, leha re sa ka ra bona phapang e joalo ka qaleho ea bohlankana.Beyer le al. 1991). Qetellong ea bohlankana kapa boroetsana, botšehali bo na le li-neuron tsa dopaminergic tse ngata, tseo re li fepang li tlatsetsa tšebetsong ea dopamine e ntlafalitsoeng ea bong. Leha ho le joalo, litlamorao tse tlisoang ke tse fetang palo ea lisele tsa dopaminergic li ka baka ho hlaha ha phapang ea thobalano mosebetsing oa dopaminergic. Bakhethoa ba ka bang teng ba kenyelletsa ponahalo ea litla-morao tsa estradiol ho DAT le li-receptors hammoho le litlamorao tsa ts'ebetso ea androgen ho li-circuits tsa cortical neural tse kentsoeng tšebetsong ea mosebetsi o phahameng. Ntle le moo, tlatsetso e kopanetsoeng (mohlomong karabo ea GABAergic mabapi le li-neuropathy tsa dopaminergic, e bontšitsoeng karolong e ka tlase e ka lehlakoreng le letona) e kanna ea kenya letsoho taolong e eketsehileng ea mesebetsi ea dopaminergic ho basali.
Ho na le lebaka le le leng la ho fetolela bohlokoa ba liphetho tsena tsa ho lemalla. Liphetoho tse ka sehloohong tsa bongoana mabapi le ts'ebetso ea dopaminergic eo re e boneng e etsahetse dorsal striatum. Li-neuroplopathy tsa dopaminergic tse projeke e tsoang ho VTA ho isa bokong ba nyutlelie e ka ba ea bohlokoa haholo ho mokhahlelo oa pele oa ts'ebeliso ea lithethefatsi (Koob 1996; McBride et al. 1999; Di Chiara 2002). Leha ho le joalo, keketseho ea dopamine ho dorsal striatum ho nahanoa hore e bohlokoa bakeng sa phetoho ho tloha ho itlhahisa ka lithethefatsi ka boithaopo ho ithuta tloaelo, karolo ea bohlokoa ho nts'etsopele ea bokhoba ba tahi (Vanderschuren le Everitt 2004; Volkow et al. 2006; Bona et al. 2007; Dalley le Everitt 2009). Tlhaloso e 'ngoe ea liphumano tsena ke hore le ha litlamorao tsa lithethefatsi li ka' na tsa se ke tsa e-ba kholo ho feta lilemong tsa bocha, phetoho ea mekhoa e lemalloang ea boitšoaro e ka hlaha kapele ho batho ba sebelisang lithethefatsi bongoaneng.
Ho hlaha ha phapang ea thobalano mosebetsing oa dopaminergic ho ne ho phahame haholo holim'a tšusumetso e tloaelehileng ea ntlafatso. Lintlha tsena li boetse li tsamaisana le lingoliloeng tsa lefu lena tse bonts'ang hore bacha ba batona le ba batona ba kotsing e kholo ea ho leka le ho itlhahisa ka lithethefatsi tse lemalloang empa litaba tse amanang le bong le tsona lia hlaha ha bacha ba hola. Bohlokoa ba boitšoaro ba ts'ebetso ea dopaminergic e ntlafalitsoeng nakong ea bocha ho banna e lula e le potso ea bohlokoa. Na e amana le ho ba kotsing ea ho lemalla? Lithuto tsa Epidemiologic li bonts'a hore tšebeliso ea lithethefatsi ea pejana e qala (bonyenyaneng ba pelehi, qalong ea nts'etsopele ea bongaka ho banna), e kotsing e kholo ea ts'ebeliso ea lithethefatsi nakong e tlang. Ho eketseha ha testosterone ho ama joang litloaelo tsa ho nka lithethefatsi? Boithuto bo khahlisang ba hore testosterone ka boeona e tsamaisoa ka bohato ka liketso tse kenyelletsang androgens le estrogens li bontša karolo ea bohlokoa bakeng sa androgen e e-so ka e khetholloa (Wood 2004; Sato et al. 2008; Wood 2008). Lithuto tsa liphoofolo tse lekolang boits'ebetso ba lithethefatsi ho banna ba amohetseng ho fallisoa ho ka thusa ho araba lipotso tsena.
Litšusumetso tsa Endocrine ho Sisteme e Seng Dopaminergic
Tlhahlobo ena e shebile karolo e le 'ngoe ea bokhoba ba lithibelo bo ipakileng e le bohlokoa ba ho lemalla: tlhabollo ea li-neuron tsa dopaminergic tse amehang taolong ea matlafatso. Leha ho le joalo, likarolo tse ling tsa ts'ebetso ea neural e bohlokoa ho tsa bocha le tsona lia fetoha nakong ea bocha. Nako ea ts'ebetso ea botsamaisi karolong e ka pele ea cortex ho kenyelletsa litšusumetso tsa Noradrenergic le serotonergic tse amehang ka mokhoa o ts'oarellang tlhokomelo le thibelo ea boitšoaro ke liketsahalo tsa bohlokoa tsa ntlafatso ea boko ba bongoana (Litho tsa et al. 2003). Re shebile bopaki bo kaholimo ba hore androgen e laola li-circal cortex dopaminergic circuits. Ho eketseha ha testosterone nakong ea bokhachane ho ka susumetsa ts'ebetso ea "cortex" ea pele kapa bokhoni ba karabelo, empa phetoho ea li-hormone tsa "pubertal" liphetoho tse bohlokoa ho mesebetsi ena ea boko ha e so ithutoe ho batho kapa mehlaleng ea liphoofolo.
Summary
Bokhoni ba ho lemalla ho kenella bokhobeng bo tletse lilemong tsa bocha. Karolo ea bohlokoa ea tlokotsi ena e bonts'a sethala sa nts'etsopele eseng thobalano. Lithuto tsa batho li bontša hore banna le basali ba sebelisang lithethefatsi tse lemalloang bongoaneng ba na le kotsi e kholo ea ho lemalla ho feta ba qalang e le batho ba baholo. Ho theoha ho hoholo ha khokahano ea dopamine ea koae eo re e boneng e le banna le basali ba lilemong tsa bocha ho bontša hore liphetoho tsa bohlokoa tsa nts'etsopele ea li-dopaminergic li etsahala nakong ea bocha ka tsela e ikemetseng ea thobalano. Leha ho le joalo, re boetse re bonts'a hore liphapang tse hlalosoang hantle ka thobalano tšebetsong ea dopaminergic li hlaha nakong ea bohlankana, mme mohlomong li ka kenya letsoho karohanong ea thobalano mokhoeng oa ts'ebeliso ea lithethefatsi e hlahang nakong ea bongoana bathong.
lumela hore baa fokola
Ts'ehetso ea NIDA ea thuso ea DA019114 le 009079 e ananeloa ka kananelo. Liteko tsohle tsa liphoofolo li entsoe ho latela liprotheine tsa liphoofolo tse amohetsoeng ke Univesithi ea Duke.
Mongolo o botlaaseng ba leqephe
Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.
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