Maikutlo: Tlhahlobo ea e mong oa bafuputsi ba kaholimo-limo ea hlalosang kamoo meputso ea tlholeho le lithethefatsi li kenang.
Boithuto bo felletseng: Neuroscience ea Meputso ea Tlhaho e amanang le Lithethefatsi tse lemalloang
Journal ea Neuroscience, 1 Mots'eanong 2002, 22 (9): 3306-3311; Ann E. Kelley1 le Kent C. Berridge2
+ Lingoliloeng tsa Sengoli
1 Lefapha la Psychiatry, Univesithi ea Wisconsin – Madison Medical School, Madison, Wisconsin 53719, le
Lefapha la Psychology, University of Michigan, Ann Arbor, Michigan 2-48109
Selelekela
Lithethefatsi tse lemalloang li sebetsa mecheng ea moputso oa boko, leha boko bo fetohile hore bo se arabele lithethefatsi empa e le meputso ea tlhaho, joalo ka lijo le thobalano. Likarabo tse nepahetseng meputsong ea tlhaho li ne li le bohlokoa molemong oa pholoho, ho ikatisa le ho phela hantle 'meleng. Ka quirk ea pheletso ea ho iphetola ha lintho, batho ba ile ba sibolla mokhoa oa ho hlasimolla sistimi ena ka maiketsetso. Likarolo tse ngata tsa limolek'hule tsa methapo ea methapo e fanang ka moputso, le lits'ebetso tse anngoeng ke lithethefatsi tse lemalloang, li bolokiloe mefuteng eohle ho tloha Drosophilae ho ea ho likhoto ho batho mme li kenyelletsa dopamine (DA), G-protein, protein kinases, amine transporters, le lingoloa tse joalo ka protheine e tlamang karolo ea cAMP (CREB). Kutloisiso e betere ea litsamaiso tsa moputso oa bokong ba tlhaho ka hona e tla ntlafatsa kutloisiso ea lebaka la neural la bokhoba.
Li-comforter, li-drive le litsamaiso tsa khothatso
Pele ho molemo ho nahana ka tšimo e tsamaileng ka mohopolo lilemong tse mashome tsa morao tjena. Leha maikutlo a sa bonahale, lipolelo tse ngata tsa sepheo le boits'oaro, boits'oaro le karabelo ea methapo ea maikutlo li khethiloe ka ho iphetola ha lintho. Liphuputso tsa likarabo tsena tsa sepheo sa liphoofolo le batho li fana ka lifensetere tsa bohlokoa ts'ebetsong ea moputso oa boko. Likhopolo tsa pele tsa ho khanna li ne li re tlala le lenyora li bolela boits'oaro bo susumetsang ka kotloloho joalo ka ha bo khopisa le hore li matlafatso li fokolitse linaha tseo feela, ho matlafatsa litloaelo tsa karabelo ea pele (S-R) kapa ho eketsa menyetla ea ts'ebetso ea ts'ebetso ea ts'ebetso. Meputso e se e tsejoa hona joale hore e sebetse bonyane ka mokhoa oa bohlokoa joalo ka ts'usumetso ea hedonic, e bakang boemeli ba methapo e fanang ka tšusumetso le sepheo sa sepheo, eseng e le matlafatso a tloaelo. Phallo ea 'mele e re e bapala karolo ea bohlokoa molemong oa tšusumetso, empa haholo-holo ka ho eketsa boleng ba hedonic le khothatso ea moputso o tsamaellanang; mohlala, lijo li latsoeha hamonate ha u lapile, u noa ha u nyoriloe, joalo-joalo. Mohlomong ho makatsang ke hore le moputso oa lithethefatsi le ho hula ho bonahala ho susumetsa boits'oaro ba tšebeliso ea lithethefatsi haholo-holo ka metheo ea ho khothaletsa molumo ho fapana le ho otlolla ka kotloloho ka ho khanna habonolo (Stewart le Wise, 1992). Ka hona, ho hlokahala hore bo-ramahlale ba nang le tšusumetso e matla ba utloisise motheo oa methapo ea ts'usumetso ea meputso.
Mesocorticolimbic dopamine: monyaka, matlafatso, ho bolela esale pele ka moputso, boikhohomoso, kapa eng?
Ke khale ho hlokomeloe hore ho sebetsoa ha meputso ho latela litsamaiso tsa DA tsa mesocorticolimbic, tse nang le li-neuron tsa DA sebakeng sa ventral tegmental (VTA) le likhakanyo tsa bona ho li-nucleus accumbens (NAc), amygdala, prefrontal cortex (PFC), le libaka tse ling tsa forebrain. Boiteko bo boholo bo lekile ho hlakisa hore na sistimi ena e kenya letsoho mosebetsing ofe. Na mesocorticolimbic DA e buella thabo ea tšusumetso ea moputso? Sena se ile sa hlahisoa qalong hobane litsamaiso tsa mesocorticolimbic li ts'oaroa ke meputso e mengata ea tlholeho le lithethefatsi, mme thibelo ea bona e sitisa ts'ebetso ea boits'oaro ba batšehetsi ba bangata (Bohlale, 1985). Na likhakanyo tsa mesocorticolimbic li ithuta le ho noha ketsahalo ea meputso? Khopolo-taba eo e nang le tšusumetso e matla e ne e ipapisitse le bopaki ba hore li-neurons tsa DA li chesa mollo ho fana ka maikutlo a bolelang meputso empa eseng ho mehopolo ea hedonic e seng e boletsoe esale pele (Schultz, 2000). Na litsamaiso tsa DA tsa mesocorticolimbic li hokahanya bohloeki bo susumetsoang bo hlahisitsoeng ke lipontšo tsa methapo le meputso, e li bakang hore li nkoe e le lipheo tse "batloang"? Khopolo-taba ea "ho batla" khopolo eo e ne e thehiloe qalong ho bopaki ba hore mesolimbic DA ha e hlokehe ho sebetsana le tšusumetso ea hedonic kapa "ho rata" meputso e monate, kapa thuto e ncha ka bona, leha e le bohlokoa bakeng sa boits'oaro bo susumetsang ho fumana meputso e tšoanang (Berridge le Robinson, 1998). Kapa qetellong, na ho nka karolo ha mesocorticolimbic DA ho phehelleng moputso ho bonts'a mesebetsi e pharalletseng, joalo ka tlhokomelo, kopanyo e rarahaneng ea li-sensorimotor, boiteko kapa ho fetoha lipakeng tsa mananeo a boits'oaro? Mesebetsi eo e ile ea hlahisoa motheong oa maikutlo a fapaneng a sa lumellaneng habonolo le moralo o hloekileng oa moputso (Salamone, 1994; Gray et al., 1999; Ikemoto le Panksepp, 1999; Redgrave et al., 1999; Horvitz, 2000). Khopolo-taba e 'ngoe le e' ngoe e na le balateli ba eona, leha ho e-na le kananelo ea hore ba arolelana lintho tsa bohlokoa tse tšoanang, 'me tumellano mabapi le ts'ebetso ea khothatso e ka bang teng joale.
Ho fumana karabo e nepahetseng haholoanyane potsong ea hore na "DA e etsa eng ho putsa" ho bohlokoa haholo ho utloisisa ho lemalla lithethefatsi, hobane lithethefatsi tse lemalloang li lumelloa ka bophara hore li sebetse haholoholo, leha e se feela, lits'ebetsong tsa mesocorticolimbic ea boko. Mohlala, likhopolo tsa hedonic tsa bokhoba ba tahi li nahana hore litsamaiso tsa DA tsa mesocorticolimbic ka ho khetheha li buella thabo e matla ea lithethefatsi tse lemalloang le anhedonia nakong ea ho tlohela (Volkow et al., 1999; Koob le Le Moal, 2001). Likhopolo tsa bokhoba ba thuto e thehiloeng ho ho ithuta li nka mecha e matlafatsang kapa e fetotsoeng ea ho ithuta ea SR, 'me meputso ea ho bolela esale pele e baka mekhoa e metle ea ho sebelisa lithethefatsi (Di Chiara, 1998; Kelley, 1999; Berke le Hyman, 2000; Everitt et al., 2001). Khopolo ea khothatso ea ho lemalla bokhoba e nka hore ts'ebeliso ea methapo ea kutlo e baka tšusumetso e fetelletseng ea tšusumetso ho litlamorao tse amanang le lithethefatsi le liketso, tse etsang hore makhoba a qobelloe "ho batla" ho sebelisa lithethefatsi hape (Robinson le Berridge, 1993,2000; Hyman le Malenka, 2001 ).
Mabapi le menehelo ea tlhaho ea ho lemalla methapo ea kutlo, hoa hlokomeleha hore likhopolo tsohle tse kholo tsa lithuto tsa ts'ebetso ea DA tsa mesocorticolimbic li hlahisitsoe qalong motheong oa lithuto tsa moputso oa tlhaho. Ka hona, kutloisiso e betere ea seo DA e se etsang bakeng sa meputso ea tlholeho e tla hlakisa mekhoa ea boko ea ho lemalla lithethefatsi.
Mesocorticolimbic dopamine: takatso e matla khahlanong le tšusumetso e matla
Ntle le ho ba le karolo moputsong, litsamaiso tsa mesocorticolimbic le tsona li nka karolo maemong a mabe a maikutlo le ts'usumetso e matla.
Ke kamano efe e ka bang le tšusumetso e mpe (ntle le ho tlohela)? Matšoao a ferekanyang a psychosis, paranoia, kapa matšoenyeho ka linako tse ling a kenella ho batho ba lemalloang ke batho le liphoofolong tsa liphoofolo ka lithethefatsi tse kang amphetamine kapa k'hok'heine (Ettenberg le Geist, 1993), empa ke joang "tsamaiso ea moputso" ea boko le eona e ka kenyang tšusumetso e mpe le maikutlo? Maikutlo a mang a fana ka maikutlo a hore litsamaiso tsa mesocorticolimbic li etsa mesebetsi e akaretsang, joalo ka tlhokomelo kapa kopanyo ea sensorimotor, eseng ho putsa kapa ho hloea ka kotloloho (Salamone, 1994; Gray et al., 1999; Horvitz, 2000). Khopolo-taba e 'ngoe ke hore likarabo tsa DA ts'ebetsong e matlafatsang li bonts'a mekhoa ea ts'usumetso e patehileng e amehang ho phehelleng polokeho (Rada et al., 1998; Ikemoto le Panksepp, 1999), ho ipapisa le likhopolo tsa kelello tsa ho qoba ho ithuta. Ka mantsoe a mang, ho lelekisa lijo ka mafolofolo ha u lapile kapa polokeho ha u le kotsing ho ka kenyelletsa lits'ebetso tse ts'oanang tsa khothatso ea mesocorticolimbic. Leha ho le joalo, bafuputsi ba bangata ba kanna ba ts'ehetsa mohopolo oa boraro oa hore litsamaiso tse ling tsa mesocorticolimbic li bapala karolo e mafolofolo molemong oa boits'oaro ka bo tsona, ho fapana le boemeli ba DA ba moputso (Salamone, 1994; Berridge le Robinson, 1998; Gray et al., 1999).
Melao e 'maloa ea bopaki e bonts'a lipakeng tse tobileng tsa mesocorticolimbic ea ts'usumetso e matla. Litsamaiso tsa boko ba Mesocorticolimbic li sebelisoa liphoofolong le bathong ka tšusumetso e matla joalo ka khatello ea maikutlo, ho tshoha ha motlakase, jj. (Piazza et al., 1996; Becerra et al., 2001). Tsamaiso ea Amphetamine e ntlafatsa maemo a kopaneng a karabelo ea boits'oaro (Gray et al., 1999), athe liso tsa mantlha tsa NAc li senya maemo a likarabo tse fapakaneng ho likhopolo tsa Pavlovian (Parkinson et al., 1999). Tšusumetso e mpe khahlanong le moputso e ka buelloa ke liteishene tse fapaneng tsa mesocorticolimbic tsa ts'ebetso ea tlhahisoleseling. Khethollo ea valence ea Neuroanatomical le neurochemical ea valence e bonts'oa ka ho elelloa hore li-microinjection tsa GABAergic ka har'a khetla ea NAc li ka baka tšusumetso e matla kapa tšusumetso e mpe, ho latela karoloana ea khetla. Li-microinjection tsa GABA tse nang le likhetla tse kahare li etsa hore motho a be le takatso ea ho ja, empa li-microinjection tse tšoanang le khetla ea morao-rao e etsa hore ho hatakelo ho tšosang (Stratford le Kelley, 1999; Reynolds le Berridge, 2001), boitšoaro bo tloaetseng ho bolokoa ke litoeba naheng lintho tse kotsi tse kang ho tšosa linonyana (Treit et al., 1981; Coss and Owings, 1989; Owings le Morton, 1998). Tlhakiso e ngoe ea hore na mesocorticolimbic subsystems e fana ka lintlha tse nepahetseng ha e bapisoa le linaha tse khothatsang e lokela ho ba ntho ea mantlha e le mokhoa oa ho fana ka leseli la hore na hobaneng lithethefatsi tsa tlhekefetso ka linako tse ling li hlahisa litlamorao tse tsoakiloeng, ho kenyeletsoa matšoenyeho le ts'oaetso ea psychosis.
Meputso ea tlholeho joalo ka lifensetere ho moputso "ho o rata" ho bapisoa le moputso "o batlang"
Le ha ba lemaletseng lithethefatsi ba batla ho sebelisa lithethefatsi ho feta batho ba bang, ba kanna ba se rate lithethefatsi tseo ka mokhoa o ts'oanang, haholoholo haeba mamello ea neuropharmacological e hola ho ba le phello e khahlisang; leha ho le joalo, phapang lipakeng tsa litsamaiso tsa methapo ea "ho batla" moputso le "ho rata" moputso li hlahile ka ho hlaka ho tsoa liphuputsong tsa meputso ea tlholeho, haholo-holo moputso o monate oa tatso, moo ho ka khonehang ho sebelisa sefahleho se khahlisang ho lekanya "ho rata" kapa tšusumetso ea hedonic hanghang. Ho masea a batho (Setšoantšo sa 1), tatso ea sucrose e hlahisa sefahleho sa sefahleho (sefahleho sa leleme, ho bososela, jj), athe tatso ea quinine e etsa hore sefahleho sa sefahleho se "se sa rate" (gape, jj.) (Steiner et al., 2001). Papiso ea lipolelo tsa masea a batho le bonyane mefuta e 11 e meholo ea litšoene le litšoene e bontša hore lipolelo tsa mofuta oa `` primate '' bakeng sa "ho rata" le "ho se rate" li khetholloa ka ts'ebetso e matla ea ts'ebetso ho mefuta eohle le ka homology ea likarolo tsa microstructure, joalo ka taolo ea allometric ea karolo lebelo (Steiner et al., 2001). Le likhoto li bonts'a liphetoho tsena litakatsong tse bonts'ang lits'ebetso tsa mantlha tsa tšusumetso le mekhoa ea hedonic neural e ts'oanang le ea batho (Grill le Norgren, 1978; Berridge, 2000).
Setšoantšo sa 1.
Boitšoaro ba tlhaho ba liteko tsa moputso le ts'ireletso e mpe e tšosang. Ho rata sefahleho ho khahlisoa ke tatso ea sucrose ho masea a batho a sa tsoa tsoaloa, li-orangutan le likhoto [holimo ka ho le letšehali, linepe tsa sefahleho tse tsoang ho Steiner et al. (2001) le Berridge (2000)]. Lipolelo tse sa rateheng li hlahisoa ke tatso ea quinine. 'Mapa oa NAc oa li-opioid tse ratang le libaka tse batlang tefo ea lijo o bonts'a matla a lijo tse batlang li hlahisoa ke morphine microinjections ka har'a khetla [tlase letsohong le letšehali, Peciña le Berridge (2000)]. Kerafo e tsamaeang le eona e bonts'a keketseho ea liphetoho tse tšoanang le tsa sucrose tse bakiloeng ke morphine microinjections ka har'a khetla ea accumbens. Ka lehlakoreng le leng, litlamorao tsa matšoenyeho le khatello ea kelello ea lithethefatsi tse lemalloang li ka amana le tšabo ea tlhaho ea ts'ireletso (ka ho le letona). Ho hatakela ka tšabo ho tšosang ho hlaha ka tlhaho ho litoeba ke liphoofolo tse jang tse ling 'me bohareng ke GABA agonist microinjections ka caudal accumbens shell [California ground squirrel foto ea John Cooke oa Coss le Owings (1989); foto ea likhoto e tsoang ho Reynolds le Berridge (2001)]. Bar graph e bonts'a ho ts'oha ho tšabang ho itšireletsa ka har'a rostrocaudal gradient ka har'a khetla ea NAc kamora GABA agonist microinjections (Reynolds le Berridge, 2001). Ho fanoa ka methati e arohaneng ea mesocorticolimbic bakeng sa ts'ebetso e matlafatsang le e matlafatsang ke mapa a sagittal a NAc shell rostrocaudal karohano ea boits'oaro bo nepahetseng ba GABA (matšoao a anteriorx) khahlano le boits'oaro bo tšabehang ba ho itšireletsa.
Opioid peptide neurotransmission kahare ho NAc e hlophisa tšusumetso ea hedonic ea moputso oa lijo (Glass et al., 1999; Peciña le Berridge, 2000; Kelley et al., 2002), ho fana ka ts'ehetso e tsoelang pele ea hore lithethefatsi tsa tlhekefetso li sebetsa lits'ebetsong tse fetohileng ho sebetsana le tlhaho joalo. menyaka joaloka monate “o rata.” Mohlala, microinjection ea morphine ka har'a khetla ea NAc e eketsa ka kotloloho likhoto tse "ratang" kapa lipolelo tsa sefahleho tse hlahisitsoeng ke sucrose (Peciña le Berridge, 2000) le liphetoho tse fetohang tse lumellanang le phepo e ntlafalitsoeng ea lijo (Zhang le Kelley, 2000). Liphuputso tse joalo li bonts'a bohlokoa ba lits'ebetso tsa methapo ea methapo ntle le dopamine ho litlamorao tsa meputso.
Qalong ho makatsang e bile liphuputso tsa hore mesocorticolimbic DA manipulations ha e fetole "ho rata" tatso ea sucrose (Peciña et al., 1997; Wyvell le Berridge, 2000), leha ba nkile karolo ho susumelletseng "ho batla" meputso ena le e meng. Ho ikarola ha methapo ea "ho rata" ho "batla" ho na le kamano e hlakileng le ho lemalla. Khopolo-taba ea khothatso e fana ka maikutlo a hore bokhoba bo ka tšoauoa ka "ho batla" litlhare tse bakoang ke litsamaiso tse amanang le DA tse matlafalitsoeng, leha ho se na lithethefatsi "tseo u li ratang" (Robinson le Berridge, 2000; Hyman le Malenka, 2001).
Ho tloha ho li-node ho ea ho marang-rang a matla
Boitšoaro bo amanang le moputso bo hlaha mesebetsing e matla ea li-network tsa neural ho fapana le sebopeho sefe kapa sefe sa boko. Mesebetsi ea NAc, amygdala, jj., Moputsong oa tlhaho kapa bokhobeng e ka utloisisoa feela ho latela sistimi e atolositsoeng ea methapo eo ba lulang ho eona (Setšoantšo sa 2). Leha re se re na le tsebo e sebetsang ea likarolo tsa bohlokoa tsa boko ba moputso, kutloisiso e tebileng e tla hloka tlhahlobo ea litšebelisano tsa marang-rang lipakeng tsa likarolo tsa amygdala, PFC, NAc, le likarolo tse ling molemong oa moputso le tšusumetso (Kalivas le Nakamura, 1999; Rolls, 1999; Everitt le al., 2000; Schultz, 2000; Jackson le Moghaddam, 2001). Mohlala, amygdala le orbital prefrontal cortex e ka bapala karolo e tlatselletsang ho ithuteng ka moputso mabapi le ho fumana boleng ba khothatso khahlanong le khetho ea karabelo (Schoenbaum et al., 1999; Baxter et al., 2000).
Setšoantšo sa 2.
Setšoantšo sa skema ea karolo ea boko ba sagittal e bonts'ang litsela tse amehang ho sebetsaneng le meputso ea tlhaho le polasetiki ea methapo ea motheo e ithutoang e amanang le moputso. Potoloho e emeloang ka boputsoa e bontša litsela tse telele tsa glutamatergic lipakeng tsa prefrontal cortex (PFC), amygdala (Amyg), hippocampus (Hipp), ventral striatum (nucleus accumbens) le sebaka sa ventral tegmental (VTA). Potoloho e khubelu e emela litsamaiso tsa mantlha tse nyolohang tsa mesocorticolimbic dopamine. Litsela tse nang le mebala e tsamaellanang li bonts'a ho ts'oana ha DA, glutamate, le GABAergic ho dorsal striatum. substrate bakeng sa boits'oaro le boits'oaro. Bakeng sa ho nolofatsa, ha ho bontšoe lipotoloho tsohle tse amehang; mohlala, ho na le likhokahano tsa bohlokoa lipakeng tsa hypothalamus le amygdala, mme litlatsetso tsa glutamatergic thalamic ha li bontšoe. Ho taka karolo ho ipapisitse le atlelase ea Paxinos le Watson (1). Metsu e meholo e bonts'a phallo ea litsela tse sebetsanang le li-viscero-endocrine le litsamaiso tse ikemetseng (tse tsoang ho hypothalamus le amygdala) le litsamaiso tsa boithaopo tsa somatic (tse tsoang basal ganglia le ventral midbrain). polasetiki e itšetlehileng kahare ho li-node tse bontšitsoeng (violet shaded). Polasetiki e joalo, e ka lebisang tšebetsong ea marang-rang, e nahanoa hore e sebelise ho ithuta le mohopolo o tloaelehileng o amanang le meputso ea tlhaho empa hape ke karolo ea bohlokoa ea bokhoba ba tahi. AcbC, Accumbens konokono; Acb khetla, accumbens khetla; Cpu, caudate-putamen; VP, ventral pallidum; Hypo, hypothalamus; SN, boholo ba nigra. Likarolo tse ling li ka fumanoa ho Paxinos and Watson (1998).
Karolo e 'ngoe ea marang-rang e mabapi le likhakanyo tse sebetsang tsa NAc ho shebisisa likarolo tse kang lateral hypothalamus le ventral pallidum. Phallo ena e bonahala e le bohlokoa ho puisano ea NAc ea boits'oaro ba tlhaho (Kalivas le Nakamura, 1999; Stratford le Kelley, 1999; Zahm, 2000). Tlatsetso ea boitšoaro ba ho ja ka ho thibela li-spiny neurons ka har'a khetla ea NAc ho latela matšoao ho lateral hypothalamus, e sebelisang li-neuron tsa morao-rao tsa hypothalamic ka disinhibition (Rada et al., 1997; Stratford le Kelley, 1999). Kahoo, khetla ea NAc e ka fana ka tlhaiso-leseling ea corticolimbic ho lateral hypothalamus mme ea fana ka taolo e phahameng ho lipotoloho tsa boko tse laolang boitšoaro ba phepo le tšusumetso e amanang le eona (Kelley, 1999; Petrovich et al., 2001). Lenaneo lena la corticostriatal – hypothalamic – brainstem le tšoaneloa ke ho ba sepheo sa thuto e tsoelang pele, maemong a moputso le tlholeho ea tlhaho (Swanson, 2000).
Likhetho tsa Neural le khetho ea boits'oaro
Ho feto-fetoha ha matla ha boleng ba tšusumetso ho hlaha lipontšong tse fapaneng tsa marang-rang tse bakang phapang liprofinseng tsa li-spiny tsa NAc tse mahareng. Mohlala, li-neuron tsena li bonts'a linaha tse "bistable" tse ka bang teng, tse itšetlehileng ka phasic excitatory glutamatergic input e tsoang mehahong e amanang le hippocampus (O'Donnell le Grace, 1995). Li-neuron tsa NAc li nyefoloa ke ho kenya letsoho ha PFC ha li le sebakeng sa "hippocampal-gated", ka hona, synchrony ea marang-rang e hlaha lipakeng tsa NAc le hippocampus (Goto le O'Donnell, 2001). Ho ts'oaroa ho ts'oanang ha li-neuron tsa NAc ho ka hlaha lipakeng tsa lisebelisoa tsa amygdala le hippocampal (Mulder et al., 1998; Floresco et al., 2001b). Tlatsetso ea DA le eona e bapala karolo ea bohlokoa phetohong ea NAc mme e susumetsoa ke ho kenya letsoho hippocampal glutamatergic ho VTA (Legault le Wise, 2001). Kahoo, ho feto-fetoha ha molumo o matla ke matšoao a kenang a marang-rang ho ka laola hore na ke eng e susumetsang ea NAc ho tataisa boits'oaro ho moputso oa tlhaho kapa oa lithethefatsi.
Polasetiki ea marang-rang e kopantsoeng ke litšebelisano tsa DA-glutamate
Lithethefatsi tse lemalloang li ka baka ts'oaetso ea nako e telele maemong a sebopeho, lisele, limolek'hule le genomic (Hyman le Malenka, 2001), empa polasetiki e joalo e amana joang le moputso le tšusumetso ea tlhaho? Ts'ebetso e khahlisang e hlaha lipatlisisong tsa polasetiki e kopaneng ea glutamate-DA le litlamorao tsa eona tsa sengoloa. Ts'ebetso e ts'oanang ea li-receptor tsa DA D1 le li-receptor tsa NMDA tsa glutamate li bapala karolo ea bohlokoa ho theheng meralo ea synaptic le li-ensembles tsa neural tse amehang ho susumetseng le ho ithuteng.
Ho striatum le PFC ka bobeli, ts'ebetso ea ts'ebetso ea D1 e ka hlahisa likarabo tsa NMDA (Seamans et al., 2001; Wang le O'Donnell, 2001), le ts'ebeliso ea nako e telele ho hippocampal-prefrontal cortex synapses e ipapisitse le tšebelisano-mmoho ea li-receptor tsa NMDA le D1 joalo-joalo. li-cascade tsa li-intracellular tse amanang le protein kinase A (Gurden et al., 2000). Sensitization ka lithethefatsi tsa tlhekefetso e tsamaisoa ke tšebelisano e amanang ea glutamate-dopamine e bakoang ke ha lithethefatsi li fanoa tikolohong e fapaneng e fapaneng (Uslaner et al., 2001). Ho bokelleng methapo ea kutlo, ts'ebetso ea tšebelisano-'moho ea li-receptor tsa D1 le NMDA e kopanya mesebetsi ea hippocampal-evoke spiking (Floresco et al., 2001b), 'me synergism e ts'oanang e ea bonoa bakeng sa tsela ea amygdalo-accumbens (Floresco et al., 2001a). Liphuputso tsa limolek'hule li tlatselletsa liphuputso tsena, li bonts'a ts'ehetso ea NMDA-receptor ea ph1 phosphorylation ea D1996-mediated ea CREB (Konradi et al., 1997; Das et al., 1), sengoloa sa sengoloa se nahanoang e le modulator e bolokileng mekhoa ea mohopolo. Litholoana tsa sengoloa tsa khokahanyo ea NMDA le D2000 mokokotlong oa NAc le PFC lia hlokahala bakeng sa ho ithuta ho khotsofatsa ka lintlha, meputso le liketso tsa boits'oaro, haholo-holo maemong a pele a ho fumana (Baldwin et al., 2002, 2000a, b; Smith-Roe le Kelley, 1). Ka kakaretso, ts'ebetso e hokahaneng ea lits'ebetso tsa DA DXNUMX le NMDA ka har'a lipotoloho tsa corticolimbic-striatal ke karolo ea bohlokoa ea ho ithuta ka moputso o feto-fetohang.
Pale ena e fana ka maikutlo a hore lithethefatsi tsa tlhekefetso tse lebisang ho DA le glutamate synapses li lokela ho mamella mesebetsi ea mantlha ea lisele le limolek'hule. Polasetiki e joalo e tšoarellang nako e telele ea methapo ea methapo e bakoang ke lithethefatsi e ka tlatsetsa ho sebetsaneng le tlhaiso-leseling e sa tloaelehang ea tlhaiso-leseling, ho baka ho etsa liqeto tse fosahetseng, tahlehelo ea taolo, le ho qobelloa ho khethollang bokhoba. Lithethefatsi tseo tsa tlhekefetso li baka likhakanyo tsa D1- le NMDA-mediated neuronal tse arolelanoeng le ho ithuta ka moputso o tloaelehileng ke temohisiso ea bohlokoa mabapi le bokhoba bo hlahileng lilemong tse leshome tse fetileng.
Moputso kantle ho netweke ea setso ea limbic?
Le ha ho ithutiloe hanyane, moputso o ka sebetsoa ka mokhoa o hlakileng mehahong ea boko eo ka tloaelo e sa nkoang e le mesocorticolimbic, e susumetsang kapa e amanang le bokhoba. Mohlala, libaka tsa "motor" tsa caudate-putamen li na le li-neuron tse arabelang lijong le lino tse susumetsang moputso, ka mokhoa o ts'oanang le oa DAergic kapa ventral striatal neurons (Aosaki et al., 1994; Schultz, 2000). Ho ja ho ka hlahisoa ka likhoto ka kotloloho ke li-microinjection tsa li-opioid agonists libakeng tsena tsa makoloi tsa dorsal striatum (Zhang le Kelley, 2000). Ho ja ho sitisoa ke ho amoheloa ha li-receptor tsa DA kapa liso libakeng tse ts'oanang le tse ling tsa bo-ntate (Cousins le Salamone, 1996). Libaka tsa Sensorimotor tsa striatum li etsa liphetoho tse matla nakong ea boithuto ba "tloaelo" (Jog et al., 1999), mme tšenyo ea bona e sitisa ho ithuta (Packard le White, 1990). Bopaki bo joalo bo fana ka maikutlo a hore likarolo tsa "sensorimotor" li ka nka karolo mesebetsing ea moputso oa tlhaho ho isa tekanyong e makatsang (White, 1989). Haeba ho joalo, ts'ebetso e joalo e atolositsoeng ea moputso e na le moelelo oa ho lemalla.
fihlela qeto e
Lithethefatsi li ka ama mekhoa ea moputso oa boko ba tlhaho ho hlahisa lithethefatsi ka mekhoa e meraro feela. (1) Meputso ea lithethefatsi e ka etsa hore tsamaiso e tšoanang ea boko e be meputso e matla ea tlhaho. Likhopolo tsa bokhoba bo ipapisitseng le lithethefatsi tse khahlisang tsa hedonia kapa ts'ehetso e nepahetseng li nahana hore lithethefatsi li sebetsa joalo ka meputso ea tlhaho. (2) Meputso ea lithethefatsi tse lemalloang e kanna ea fetola ho eketseha ha bongata ba likarolo tse ling tsa moputso, ho arohana le ho sotha lits'ebetso tse tloaelehileng tsa meputso ho baka boitšoaro bo qobelloang. Likhopolo tsa bokhoba ba lithethefatsi tse ipapisitseng le ts'ehetso ea ts'usumetso ea ts'oaetso li fana ka maikutlo a hore lithethefatsi li matlafatsa mesocorticolimbic substrates tsa ts'usumetso e matla, e arola moputso oa tlhaho ka ho matlafatsa "ho batla" ka mokhoa o sa lumellaneng ho baka boitšoaro bo qobelloang ba tšebeliso ea lithethefatsi (Robinson le Berridge, 2000; Hyman le Malenka, 2001). Likhopolo tsa bokhoba bo ipapisitseng le tšebelisano-mmoho ea nako e telele kapa liphetoho mokhoeng oa ho ithuta li hlahisa mekhoa e metle ea ho noa lithethefatsi (O'Brien et al., 1992; Di Chiara, 1998; Robbins le Everitt, 1999; Berke le Hyman, 2000; Everitt le al., 2001). (3) Lithethefatsi tse lemalloang li ka baka tšebetso e ncha ea boko, joalo ka maemo a ho ikhula, a ka bapalang likarolo tse kholo tsa ts'ebetso ea bahanyetsi ho feta tahlehelo e tloaelehileng (Solomon le Corbit, 1974; Koob le Le Moal, 2001).
Menyetla ena e meraro e felletse empa ha e tšoane. Ho fumanoe lintlha tse ngata tse khahlisang tse bonesang tšebelisano ea tsona. Liphuputso tsa nako e tlang li tla hlakisa hape hore na lithethefatsi li sebelisana joang le meputso ea boko ho hlahisa tšusumetso e tlamang le ho khutlela morao e khethollang bokhoba.
Mongolo o botlaaseng ba leqephe
• Mosebetsi ona o ne o tšehelitsoe ke Grants DA09311, DA04788, le DA13780 ho tsoa Setsing sa Naha sa Tlhekefetso ea Lithethefatsi (AEK) le IBN 0091611 ho tsoa ho National Science Foundation (KCB). Re leboha Terry Robinson, Sheila Reynolds, Matthew Andrzejewski, le Susana Peciña bakeng sa litlhahiso tse thusang mabapi le buka ena e ngotsoeng ka letsoho.
• Ngollano e lokela ho lebisoa ho AE Kelley, Lefapha la Psychiatry, University of Wisconsin – Madison Medical School, 6001 Research Park Boulevard, Madison, WI 53719. E-mail:[imeile e sirelelitsoe].
• Copyright © 2002 Mokhatlo oa Neuroscience
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