Amagqabantshintshi: Uphononongo olwenziwe ngomnye wabaphandi abaphezulu abachaza indlela imbuyekezo yendalo kunye neziyobisi ezidibana ngayo.
Isifundo esipheleleyo: I-Neuroscience yeMvuzo yeNdalo eNxulumene neDrugs Addictive
I-Journal ye-Neuroscience, i-1 ngoMeyi 2002, i-22 (9): 3306-3311; U-Ann E. Kelley1 kunye noKent C. Berridge2
+ Ukubambisana Kwombhali
Isebe le-Psychiatry eli-1, iYunivesithi yaseWisconsin-Madison Medical School, eMadison, eWisconsin 53719, kunye
2 iSebe lePsychology, iYunivesithi yaseMichigan, Ann Arbor, Michigan 48109-1109
intshayelelo
Iziyobisi ezikhobokisayo zisebenza kwiinkqubo zokuvuza kwengqondo, nangona ingqondo yavela ukuba ingaphenduli kumachiza kodwa kwimbuyekezo yendalo, njengokutya kunye nesondo. Iimpendulo ezifanelekileyo kwimbuyekezo yendalo zazibalulekile ngokuzivelelayo ukuze umntu aphile, avelise kwakhona, kunye nokomelela. Kwi-quirk yelishwa lendaleko, abantu baye bafumanisa indlela yokuvuselela le nkqubo ngokwenziwa ngamachiza. Iimpawu ezininzi zeemolekyuli zeenkqubo ze-neural ezivuselela umvuzo, kunye nezo nkqubo zichatshazelwa ziziyobisi, zigcinwa kuzo zonke iintlobo ukusuka kwiDrosophilae ukuya kwiimpuku ebantwini kwaye zibandakanya i-dopamine (DA), iiprotheyini ze-G, iprotein kinases, abathuthi be-amine, kunye nezinto ezikhutshelweyo ezifana Iprotheyini yokubopha iprotheni ye-cAMP (CREB). Ukuqonda ngcono iinkqubo zomvuzo wengqondo yendalo ke ngoko kuya konyusa ukuqonda kwe-neural causation yokulutha.
Iziqinisekiso, iidrive, kunye neenkqubo zenkuthazo
Okokuqala kuluncedo ukuqwalasela indlela intsimi ehambe ngayo ngokwengqiqo kumashumi eminyaka akutshanje. Nangona iimvakalelo zingabonakali, iinkcazo ezininzi zenjongo kunye nokuziphatha, i-physiological, kunye neempendulo ze-neural kwi-stimuli yeemvakalelo ziye zakhethwa ngokuziphendukela kwemvelo. Izifundo zezi mpendulo zenjongo kwizilwanyana kunye nabantu zibonelela ngeefestile ezixabisekileyo ekusebenzeni komvuzo wobuchopho. Iithiyori zokuqhuba kwangethuba zibambe ukuba indlala kunye nonxano luchaza indlela yokuziphatha ekhuthazayo ngokuthe ngqo njengee-aversive drive states kwaye abomelezi bawanciphisa ngokulula loo mazwe, ukomeleza imikhwa yangaphambili ye-stimulus-response (S-R) okanye ukwandisa amathuba okukhutshwa kwempendulo esebenzayo. Imbuyekezo yamkelwa ngoku ukuba isebenze ngokubaluleke kakhulu njengenkuthazo ye-hedonic, ebangela ukumelwa kwe-neural evuselela inkuthazo kunye nosukelo losukelo, endaweni yokuba nje baqinise umkhwa. I-Physiological drive states nangona kunjalo idlala indima ebalulekileyo kwinkuthazo yenkuthazo, kodwa ngokuyinhloko ngokwandisa i-hedonic kunye nexabiso lenkuthazo lomvuzo ohambelanayo; umzekelo, ukutya kunencasa bhetele xa ulambile, ukusela xa unxaniwe, njalo njalo. Mhlawumbi okumangalisayo kukuba, kwanomvuzo weziyobisi kunye nokurhoxa kubonakala kukhuthaza indlela yokuziphatha ethatha iziyobisi ngokuyintloko ngemigaqo yokukhuthaza uhlengahlengiso kunokuba ngokuthe ngqo nge-aversive drives (uStewart kunye noBulumko, 1992). Ngokufanelekileyo, kufanelekile ukuba iingcali ze-neuroscientists ziqonde isiseko se-neural sepropathi yenkuthazo yemivuzo.
I-Mesocorticolimbic dopamine: uyolo, ukomeleza, ukuxela kwangaphambili umvuzo, inkuthazo yenkuthazo, okanye yintoni?
Kudala isaziwa ukuba ukusetyenzwa komvuzo kuxhomekeke kwiinkqubo ze-mesocorticolimbic ze-DA, ezibandakanya i-DA neurons kwindawo ye-ventral tegmental (VTA) kunye noqikelelo lwabo kwi-nucleus accumbens (NAc), i-amygdala, i-prefrontal cortex (PFC), kunye neminye imimandla yangaphambili. Iinzame ezinkulu zizamile ukucacisa ukuba nguwuphi umsebenzi onegalelo kule nkqubo. Ngaba i-mesocorticolimbic DA ilamla ulonwabo lokuvuselela umvuzo? Oku kwakucetyisiwe kwasekuqaleni ngenxa yokuba iinkqubo ze-mesocorticolimbic zenziwa zisebenze yimbuyekezo emininzi yendalo kunye neziyobisi, kwaye ibhlokhi yabo iyonakalisa ukusebenza kakuhle kokuziphatha kwabaninzi abaqinisayo (Bulumko, 1985). Ngaba uqikelelo lwe-mesocorticolimbic endaweni yoko lufunda kwaye luqikelele ukwenzeka kwemivuzo? Loo hypothesis enempembelelo yonxulumano yayisekwe kubungqina bokuba i-DA neurons ivutha umlilo kwimixholo exela kwangaphambili imivuzo kodwa ingekuko ukuba sele ixelwe kwangaphambili ngemivuzo ye-hedonic (Schultz, 2000). Ngaba iinkqubo ze-DA ze-mesocorticolimbic zilamla inkuthazo ebangelwa kukubonakaliswa kwe-neural yemivuzo kunye neempawu, ezibangela ukuba zibonwe njengeenjongo "ezifunwayo"? Loo ngcamango yenkuthazo "yokufuna" yayisekelwe kubungqina bokuba i-DA ye-mesolimbic ayidingeki ukulamla impembelelo ye-hedonic okanye "ukuthanda" imivuzo emnandi, okanye ukufunda okutsha ngabo, ngaphandle kokubaluleka kokuziphatha okukhuthazwayo ukufumana imbuyekezo efanayo (iBerridge kunye Robinson, 1998). Okanye okokugqibela, ngaba ukubandakanyeka kwe-DA ye-mesocorticolimbic ekufuneni umvuzo kubonakalisa imisebenzi ebanzi, njengokuqwalaselwa, ukudityaniswa kwe-sensorimotor entsonkothileyo, umzamo, okanye ukutshintsha phakathi kweenkqubo zokuziphatha? Loo misebenzi yacetywa ngesiseko semigqaliselo eyahlukeneyo engahambelani lula nesakhelo somvuzo ococekileyo (Salamone, 1994; Grey et al., 1999; Ikemoto kunye nePanksepp, 1999; Redgrave et al., 1999; Horvitz, 2000). Ingqikelelo nganye inabalandeli bayo, nangona kukho ukuqondwa ukuba babelana ngezinto ezifanayo ezibalulekileyo, kwaye imvumelwano malunga nomsebenzi wenkuthazo okhuthazayo inokwakheka ngoku.
Ukufumana impendulo echanekileyo ngakumbi kumbuzo othi "yenza ntoni i-DA emvuzweni" kubaluleke kakhulu ekuqondeni umlutha, kuba iziyobisi ezikhobokisayo zivunyelwene ngokubanzi ukuba zisebenze ngokukodwa, nangona kungekuphela, kwiinkqubo ze-mesocorticolimbic zobuchopho. Ngokomzekelo, iithiyori ze-hedonic zokulutha zicinga ukuba iinkqubo ze-DA ze-mesocorticolimbic ikakhulu zilamla ulonwabo olukhulu lweziyobisi kunye ne-anhedonia ngexesha lokurhoxa (Volkow et al., 1999; Koob kunye noLe Moal, 2001). Iithiyori ezisekelwe ekufundeni zithatha ulwamvila okanye zitshintshwe iindlela zeselula zokufunda ngokudibeneyo kwe-SR, kwaye uqikelelo lomvuzo lubangela imikhwa yokusela iziyobisi (Di Chiara, 1998; Kelley, 1999; Berke kunye noHyman, 2000; Everitt et al., 2001). Ithiyori yenkuthazo ye-incentive-sensitization ye-addiction ithatha ukuba i-neural sensitization ibangela ukubonakaliswa okugqithisileyo kwe-incentive salience kwi-stimuli ehambelana neziyobisi kunye nezenzo, ezenza ukuba abakhoboki bafune "ukufuna" ukuthatha iziyobisi kwakhona (uRobinson noBerridge, 1993,2000; uHyman noMalenka, 2001, XNUMX) ).
Ngokumalunga namagalelo omvuzo wendalo kwi-neuroscience, kuyaphawuleka ukuba zonke iingqikelelo eziphambili zezifundo ze-mesocorticolimbic ze-DA zazicetywayo ngokwesiseko sezifundo zomvuzo wendalo. Ke ngoko, ukuqonda ngcono okwenziwa yi-DA ngembuyekezo yendalo kuya kucacisa iindlela zobuchopho zokukhotyokiswa ziziyobisi.
I-Mesocorticolimbic dopamine: ulangazelelo oluchasene nenkuthazo
Ngaphandle kokuba nendima emvuzweni, iinkqubo ze-mesocorticolimbic zikwathatha inxaxheba kwiimeko zeemvakalelo ezingathandekiyo kunye nenkuthazo eguqukayo.
Bubuphi ubudlelwane obunokuba nenkuthazo engalunganga (ngaphandle kokurhoxa) ekubeni likhoboka? Iimpawu eziguqukayo zengqondo, i-paranoia, okanye ixhala ngamanye amaxesha ziye zixhaphake kubantu abakhotyokisiweyo nakwiimodeli zezilwanyana ngamachiza anje nge-amphetamine okanye i-cocaine (Ettenberg kunye neGeist, 1993), kodwa "inkqubo yomvuzo" yobuchopho ingakwazi njani ukulamla inkuthazo engalunganga kunye neemvakalelo? Ezinye iingqikelelo zicebisa ukuba iinkqubo ze-mesocorticolimbic zilamla imisebenzi eqhelekileyo, njengokuqwalaselwa okanye ukudityaniswa kwe-sensorimotor, kwaye hayi umvuzo okanye ukucaphukela ngokuthe ngqo (Salamone, 1994; Grey et al., 1999; Horvitz, 2000). Enye i-hypothesis kukuba iimpendulo ze-DA kwi-aversive motivation zibonisa iindlela ezifihlakeleyo zenkuthazo ezibandakanyekayo ekufuneni ukhuseleko (Rada et al., 1998; Ikemoto kunye nePanksepp, 1999), ukuzoba kwiithiyori zengqondo zokufunda ukuphepha. Ngamanye amazwi, ukufuna ngokusebenzayo ukutya xa ulambile okanye ukhuselekile xa usengozini kunokubandakanya iinkqubo ezifanayo zenkuthazo ye-mesocorticolimbic. Nangona kunjalo, uninzi lwabaphandi mhlawumbi bayayixhasa i-hypothesis yesithathu yokuba iinkqubo ezithile ze-mesocorticolimbic zidlala indima esebenzayo kwi-aversive motivation ngokwayo, eyahlukileyo kulamlo lwe-DA lomvuzo. (Salamone, 1994; Berridge noRobinson, 1998; Grey et al., 1999).
Imigca emininzi yobungqina ibonisa ulamlo oluthe ngqo lwe-mesocorticolimbic lwe-aversive motivation. Iinkqubo zobuchopho ze-Mesocorticolimbic zenziwe zisebenze kwizilwanyana nakubantu ngokuvuselela i-aversive ezifana noxinzelelo, ukutshatyalaliswa kombane, njl. (Piazza et al., 1996; Becerra et al., 2001). Ulawulo lwe-Amphetamine luphucula imeko yokujongana neempendulo zokuziphatha (iGrey et al., 1999), ngelixa izilonda ze-NAc ezingundoqo ziphazamisa imeko yeempendulo eziphikisayo kwi-Pavlovian cues (Parkinson et al., 1999). Inkuthazo engalunganga xa ithelekiswa nomvuzo inokulamlwa ziindlela ezahlukeneyo ze-mesocorticolimbic zokusetyenzwa kolwazi. Ulwahlulo lwe-Neuroanatomical kunye ne-neurochemical ye-valence luboniswa ngoqwalaselo lokuba i-GABAergic microinjections kwiqokobhe le-NAc inokuvelisa nokuba yintshukumisa enamandla okanye inkuthazo engalunganga, kuxhomekeke kwi-subregion yeqokobhe. I-GABA i-agonist microinjections kwiqokobhe le-medial elingaphakathi zenza umdla wokutya, kodwa ii-microinjections ezifanayo kwiqokobhe le-medial yangasemva zenza ukhuseleko olukhuselayo lunyathelwe (iStratford kunye noKelley, 1999; uReynolds kunye noBerridge, 2001), indlela yokuziphatha edla ngokugcinwa ziimpuku endle. izinto eziphazamisayo ezinjengokusongela i-rattlesnakes (Treit et al., 1981; Coss and Owings, 1989; Owings and Morton, 1998). Ingcaciso eyongezelelekileyo malunga nendlela i-mesocorticolimbic subsystems ikhowudi ngayo, ngokuchaseneyo namazwe akhuthazayo, kufuneka ibe yeyona nto iphambili njengendlela yokucacisa ukuba kutheni amachiza okuxhatshazwa ngamanye amaxesha evelisa iziphumo ezikhuthazayo, kubandakanya ukuxhalaba kunye nokuba sengozini kwengqondo.
Imbuyekezo yendalo njengeefestile kumvuzo "ukuthanda" ngokuchasene nomvuzo "ukufuna"
Nangona amakhoboka eziyobisi efuna ukuthatha iziyobisi ngaphezu kwabanye abantu, asenokungawathandi ngokulinganayo loo machiza ngakumbi, ngakumbi ukuba ukunyamezela kwe-neuropharmacological kukhula ukuya kwimpembelelo eyolisayo; nangona kunjalo, ulwahlulo phakathi kweenkqubo ze-neural "zokufuna" umvuzo kunye "nokuthanda" umvuzo ziye zavela ngokucacileyo kwizifundo zembuyekezo yendalo, ngakumbi umvuzo wencasa emnandi, apho kunokwenzeka ukusebenzisa imbonakalo yobuso obuchaphazelekayo ukulinganisa ngokukhawuleza "ukuthanda" okanye impembelelo ye-hedonic. Kwiintsana ezingabantu (umzobo 1), incasa yesucrose ivelisa iseti yembonakalo yobuso “yokuthanda” (ukuphuma kolwimi, uncumo, njl.njl), kanti incasa yequinine ivuselela “ukungathandi” ebusweni (i-gape, njl.) (Steiner et al., 2001). Uthelekiso lwentetho yeentsana zabantu kunye nezobuncinci ezili-11 zenkawu ezinkulu kunye neentlobo zenkawu zibonisa ukuba iipatheni zokubonisa iprimate "ukuthanda" kunye "nokungathandi" ziphawulwa ngokuqhubekeka okuqinileyo kwetaxonomic kuzo zonke iintlobo kunye ne-homology yeempawu ze-microstructure, ezinjengolawulo lwe-allometric yecandelo. isantya (Steiner et al., 2001). Nditsho neempuku zibonisa oku kusabela kwiincasa ezibonisa iinkqubo ezichaphazelayo kunye neendlela ze-hedonic neural homologous kwezo zabantu (Grill noNorgren, 1978; Berridge, 2000).
Umzobo 1.
Iimvavanyo zokuziphatha ngokwendalo zokuthanda umvuzo kunye nokhuseleko olubi olunoloyiko. Ukuthanda inkangeleko yobuso kubangelwa yincasa yesucrose evela kwiintsana ezisanda kuzalwa, ii-orangutan, kunye neempuku [phezulu ekhohlo, iifoto zobuso zikaSteiner et al. (2001) kunye neBerridge (2000)]. Ukungathandi ukuthetha kubangelwa yincasa yequinine. Imephu ye-coronal ye-NAc yokuthanda i-opioid kunye nokufuna iisayithi zomvuzo wokutya ibonisa ubunzulu bokufuna ukutya okuveliswe yi-morphine microinjections kwiqokobhe [emazantsi ekhohlo, ePeciña naseBerridge (2000)]. Igrafu ekhaphayo ibonisa ukwanda kweempendulo zokuthanda i-sucrose ezibangelwa yi-morphine microinjections kwiqokobhe le-accumbens. Kwelinye icala, i-anxiogenic and psychotic iziphumo zeziyobisi ezikhobokisayo zinokunxulunyaniswa noloyiko lwendalo olusebenzayo lokuzikhusela (ekunene). Ukunyathela ngoloyiko lokuzikhusela kutsalwa ngokwemvelo kwiimpuku ngamarhamncwa e-rattlesnake kwaye embindini yi-GABA agonist microinjections kwiqokobhe le-caudal accumbens [ifoto yaseCalifornia yomhlaba we-squirrel nguJohn Cooke wase-Coss and Owings (1989); ifoto yeempuku evela eReynolds naseBerridge (2001)]. Igrafu yebha ibonisa ukunyathela ngoloyiko lokuzikhusela ecaleni kwe-rostrocaudal gradient kwiqokobhe le-NAc emva kwe-GABA agonist microinjections (Reynolds kunye neBerridge, 2001). Izahlulo ezahlukeneyo zetshaneli ze-mesocorticolimbic zemisebenzi yomnqweno kunye ne-aversive yenkuthazo icetyiswa yimephu ye-sagittal ye-NAc iqokobhe le-rostrocaudal ulwahlulo lwe-GABA-eyenziwe ngokuziphatha okuhle kokutyisa (iisimboli ze-anteriorx) ngokuchasene nokuziphatha koloyiko lokuzikhusela (izikwere ezingasemva).
I-opioid peptide neurotransmission ngaphakathi kwe-NAc imodareyitha impembelelo ye-hedonic yomvuzo wokutya (Iglasi et al., 1999; Peciña kunye noBerridge, 2000; uKelley et al., 2002), ukubonelela ngenkxaso eyongezelelweyo yokuba iziyobisi zokusetyenziswa kakubi kweenkqubo zivele ukuze zilamle indalo enjalo. ubumnandi njengobumnandi "ukuthanda." Umzekelo, i-microinjection ye-morphine kwiqokobhe le-NAc inyusa ngokuthe ngqo i-rat "ukuthanda" imbonakalo ye-orofacial efunwa yi-sucrose (i-Peciña kunye ne-Berridge, i-2000) kunye nokutshintsha ukungenisa okuhambelana nokwandiswa kokutya (uZhang noKelley, i-2000). Iziphumo ezinjalo zibonisa ukubaluleka kweenkqubo ze-neurochemical ngaphandle kwe-dopamine kwimpembelelo ye-hedonic yemivuzo.
Okwakumangalisa okokuqala kukufumanisa ukuba i-mesocorticolimbic DA manipulations ayitshintshi "ukuthanda" incasa ye-sucrose. (Peciña et al., 1997; Wyvell and Berridge, 2000), nangona indima yabo ekukhuthazeni "ukufuna" kwezi kunye neminye imivuzo. I-neurochemical dissociation "yokuthanda" ukusuka "ekufuneni" inokubaluleka okucacileyo kumlutha. Ithiyori yenkuthazo-yokuvuselela icebisa ukuba umlutha unokubonakaliswa kukwanda "kokufuna" kweziyobisi ezibangelwa ziinkqubo ezinxulumene ne-DA, nokuba akukho "ukuthanda" kweziyobisi (URobinson noBerridge, i-2000; uHyman noMalenka, i-2001).
Ukusuka kwiindawo ukuya kwiinethiwekhi eziguqukayo
Ukuziphatha okunxulumene nomvuzo kuvela kumsebenzi oguquguqukayo wothungelwano lwe-neural yonke kunokuba luvela kuso nasiphi na isakhiwo sobuchopho. Imisebenzi ye-NAc, i-amygdala, njl., kumvuzo wendalo okanye umlutha unokuqondwa kuphela ngokwenkqubo ye-neural eyandisiweyo apho bahlala khona (Umfanekiso 2). Nangona ngoku sinolwazi olusebenzayo lwezakhiwo eziphambili zobuchopho zomvuzo, ukuqonda okunzulu kuya kufuna ukuvavanywa konxibelelwano lwenethiwekhi phakathi kwe-amygdala, PFC, NAc, kunye nezinye izakhiwo kumvuzo kunye nenkuthazo (Kalivas kunye noNakamura, 1999; Rolls, 1999; Everitt; et al., 2000; Schultz, 2000;Jackson kunye noMoghaddam, 2001). Umzekelo, i-amygdala kunye ne-orbital prefrontal cortex inokudlala indima ehambelanayo ekufundeni ngomvuzo malunga nokufumana ixabiso lenkuthazo ye-cue ngokuchasene nokukhetha impendulo (Schoenbaum et al., 1999; Baxter et al., 2000).
Umzobo 2.
Ukumelwa okucwangcisiweyo kwecandelo lesagittal yobuchopho bempuku ebonisa iindlela ezibandakanyekayo ekusetyenzweni kwemivuzo yendalo kunye neplastiki ye-neural esisiseko sokufunda okunxulumene nomvuzo. I-circuitry emelwe ngeblue ibonisa iindlela ezinde ze-glutamatergic phakathi kwe-prefrontal cortex (PFC), i-amygdala (Amyg), i-hippocampus (i-Hipp), i-ventral striatum (i-nucleus accumbens), kunye ne-ventral tegmental area (VTA). Isekethe ebomvu imele ephambili enyukayo ye-mesocorticolimbic dopamine iinkqubo. Iindlela ezihlayo ezihlayo zibonisa ngokuyintloko iinkqubo ze-GABAergic ezihlayo.Iinxantathu ezinemibala ehambelanayo zibonisa i-DA efanayo, i-glutamate, kunye ne-GABAergic coding kwi-dorsal striatum.Iibhokisi ezinomthunzi we-Violet zimela iindawo ezibalulekileyo ngaphakathi kolu nxibelelwano lusasazwayo apho i-NMDA/D1 receptor-mediated plasticity icetywayo ukuba ibe yinto ebalulekileyo. isubstrate yokulungelelanisa indlela yokuziphatha nokufunda. Ngeenjongo zokulula, ayizizo zonke iisekethe ezifanelekileyo eziboniswayo; umzekelo, kukho unxibelelwano olubalulekileyo phakathi kwe-hypothalamus kunye ne-amygdala, kwaye i-glutamatergic thalamic inputs ayiboniswa. Umzobo wecandelo usekelwe kwiatlasi yePaxinos noWatson (1998). Iintolo ezinkulu zibonisa ukuhamba kweendlela ezisebenzayo eziguqukayo kwiinkqubo ze-viscero-endocrine kunye ne-autonomic (ephuma kwi-hypothalamus kunye ne-amygdala) kunye neenkqubo ze-somatic voluntary motor (eziphuma kwi-basal ganglia kunye ne-ventral midbrain). -iplastiki exhomekeke ngaphakathi kweendawo ezibonakalisiweyo (violet shaded). Iplastiki enjalo, enokuthi ibangele umsebenzi wenethiwekhi otshintshiweyo, icingelwa ukuba ilamle ukufunda okuqhelekileyo kunye nememori ehambelana nemivuzo yendalo kodwa ikwayinxalenye ephambili yokulutha. AcbC, Accumbens core;Acb iqokobhe, accumbens iqokobhe; Cpu, caudate–putamen; I-VP, i-ventral pallidum;I-Hypo, i-hypothalamus; SN, substantia nigra. Ezinye izifinyezo zinokufumaneka kwi-Paxinos kunye neWatson (1998).
Olunye uthungelwano uphawu luchaphazela uqikelelo olusebenzayo lwe-NAc ekujoliswe kulo njenge-hypothalamus esecaleni kunye ne-ventral pallidum. Oku kuphumayo kubonakala kubalulekile kulamlo lwe-NAc lokuziphatha kwemvelo (i-Kalivas kunye noNakamura, i-1999; iStratford kunye ne-Kelley, i-1999; i-Zahm, i-2000). Ukunyanzelwa kokuziphatha kokutya ngokuthintelwa kwe-spiny neurons kwiqokobhe le-NAc kuxhomekeke kwimiqondiso kwi-hypothalamus esecaleni, eyenza i-lateral hypothalamic neurons nge-disinhibition (Rada et al., 1997; Stratford kunye neKelley, 1999). Ke, iqokobhe le-NAc linokungena ulwazi lwe-corticolimbic kwi-hypothalamus esecaleni kwaye isebenzise ulawulo olulawulayo kwiisekethe zobuchopho ezilawula indlela yokuziphatha yokondla kunye nenkuthazo ehambelana nayo (Kelley, 1999; Petrovich et al., 2001). Le nethiwekhi ye-corticostriatal-hypothalamic-brainstem ifanele ukuba kugxilwe kufundo oluqhubekayo, kwiimeko zomvuzo wendalo kunye nokulutha (Swanson, 2000).
I-Neural ensembles kunye nokukhethwa kokuziphatha
Ukumodareyitha okuguquguqukayo kwexabiso lenkuthazo kuvela kwiimpawu zothungelwano ezihlukeneyo ezibangela ukuguquguquka kumazwe omntu ophakathi kwe-spiny NAc neurons. Umzekelo, ezi neurons zibonisa "bistable" inwebu enokubakho, exhomekeke kwigalelo le-phasic excitatory glutamatergic evela kwizakhiwo ezidibeneyo ezifana nehippocampus (O'Donnell kunye noGrace, 1995). I-neuron ye-NAc ichithwa yi-PFC igalelo xa ikwi-hippocampal-gated "up" state, kwaye ngaloo ndlela i-synchrony yenethiwekhi ivela phakathi kwe-NAc kunye ne-hippocampus (Goto kunye ne-O'Donnell, i-2001). Ukufakwa okufanayo kwe-NAc neurons kunokwenzeka phakathi kwe-amygdala kunye namagalelo e-hippocampal (uMulder et al., 1998; Floresco et al., 2001b). Igalelo le-DA likwadlala indima ebalulekileyo ekutshintsheni kwe-NAc kwaye iphenjelelwa yi-hippocampal glutamatergic igalelo kwi-VTA (Legault and Wise, 2001). Ke, ukumodareyitha okuguquguqukayo ngemiqondiso yenethiwekhi engenayo kunokulawula ukuba yeyiphi inkuthazo ye-NAc eyongamelayo ukukhokela indlela yokuziphatha kwimbuyekezo yendalo okanye yeziyobisi.
Iplastiki yenethiwekhi elamlwa lunxibelelwano lwe-DA-glutamate
Iziyobisi ezikhobokisayo zibangela i-neuroadaptations yexesha elide kwinqanaba lesakhiwo, iselula, imolekyuli, kunye ne-genomic (uHyman noMalenka, i-2001), kodwa iplastiki enjalo inxulumana njani nomvuzo wendalo kunye nenkuthazo? Udibaniso olonwabisayo luvela kwizifundo ze-glutamate-DA-mediated plasticity kunye neziphumo zayo zokukhutshelwa. Ukwenziwa kusebenze ngengozi kwee-receptors ze-DA D1 kunye ne-glutamate NMDA receptors zidlala indima ebalulekileyo ekubumbeni ulungelelwaniso lwe-synaptic kunye ne-neural ensembles ebandakanyekayo kwinkuthazo nokufunda.
Kuzo zombini i-striatum kunye ne-PFC, ukusebenza kwe-D1 kunokubangela iimpendulo ze-NMDA (i-Seamans et al., 2001; uWang no-O'Donnell, i-2001), kunye nokubakho kwexesha elide kwi-hippocampal-prefrontal cortex synapses kuxhomekeke kwi-coactivation ye-NMDA kunye ne-D1 receptors kunye ne-D2000. i-intracellular cascades ebandakanya iprotein kinase A (Gurden et al., 2001). Ukuqonda ngeziyobisi zokuxhatshazwa kuququzelelwa yintsebenziswano enxulumene ne-glutamate-dopamine ebangelwa xa iziyobisi zilawulwa kwindawo enoveli eyahlukileyo (Uslaner et al., 1). Kwi-accumbens neurons, isenzo sentsebenziswano yazo zombini i-D2001 kunye ne-NMDA i-receptors idibanisa umsebenzi we-hippocampal-evoked spiking (Floresco et al., 2001b), kunye ne-synergism efanayo ibonwa kwindlela ye-amygdalo-accumbens (Floresco et al., 1a). Izifundo zeemolekyuli zincedisa ezi ziphumo, zibonisa ukuxhomekeka kwe-NMDA-receptor ye-D1996-mediated phosphorylation ye-CREB (Konradi et al., 1997; Das et al., 1), into ebhaliweyo ecinga ukuba yimodyuli egcinwe ngokuguquguqukayo yeenkqubo zememori. Iziphumo zokubhaliweyo ze-NMDA kunye ne-D2000 yokubambisana kwi-NAc core kunye ne-PFC ziyimfuneko ekufundeni okukhangayo malunga neempawu, imivuzo, kunye nezenzo zokuziphatha, ngakumbi kumanqanaba okuqala okufunyanwa (uBaldwin et al., 2002, 2000a,b; Smith-Roe noKelley, 1). Lilonke, ukusebenza ngokulungelelanisiweyo kwe-DA DXNUMX kunye neenkqubo ze-NMDA ngaphakathi kweesekethe ze-corticolimbic-striatal luphawu olubalulekileyo lokufunda okuvuzwayo.
Eli bali licebisa ukuba iziyobisi zokuxhatshazwa ezijolise kwi-DA kunye ne-glutamate synapses kufuneka zitshintshe ngokuqhubekayo imisebenzi esisiseko yeselula kunye ne-molecular. Iplastikhi ehlala ixesha elide kumvuzo we-neuron eyenziwa ngamachiza inokuba negalelo ekusetyenzweni kolwazi olungaqhelekanga kunye nokuziphatha, okukhokelela ekuthathweni kwezigqibo ezingekho mgangathweni, ukulahleka kolawulo, kunye nokunyanzeliswa okuphawula ukuba likhoboka. Ukuba iziyobisi zokuxhatshazwa zibangela i-D1- kunye ne-NMDA-mediated neuronal cascades ekwabelwana ngayo ngokufunda okuqhelekileyo komvuzo lulwazi olubalulekileyo malunga nokukhotyokiswa okuthe kwavela kule minyaka ilishumi idlulileyo.
Imbuyekezo ngaphandle kwenethiwekhi yesiqhelo ye-limbic?
Nangona kufundwe kancinci, umvuzo unokucutshungulwa kakhulu kwizakhiwo zobuchopho ezingajongwa njenge-mesocorticolimbic, ekhuthazayo, okanye enxulumene nokuba likhoboka. Umzekelo, imimandla “yemoto” ye-caudate-putamen iqulethe ii-neuron eziphendula ukutya kunye nokusela umvuzo wokuvuselela, ngendlela efana ne-DAergic okanye i-ventral striatal neurons (Aosaki et al., 1994; Schultz, 2000). Ukutya kunokufunwa kwiigundane ngokuthe ngqo nge-microinjections ye-opioid agonists kule mimandla yemoto ye-dorsal striatum (uZhang noKelley, i-2000). Ukutya kuphazanyiswa yi-DA receptor blockade okanye izilonda kwiindawo ezifanayo ze-dorsal striatal (Cousins kunye neSalamone, 1996). Imimandla ye-Sensorimotor ye-striatum ifumana utshintsho oluguquguqukayo ngexesha lokufunda "umkhwa" ovuzayo (Jog et al., 1999), kwaye umonakalo wabo uphazamisa ukufunda (uPackard kunye noMhlophe, 1990). Ubungqina obunjalo bucebisa ukuba izakhiwo ze-"sensormotor" zinokuthatha inxaxheba kwimisebenzi yomvuzo wendalo ukuya kwinqanaba elimangalisayo (White, 1989). Ukuba kunjalo, ukusetyenzwa kwembuyekezo ye-neural eyandisiweyo kuneziphumo zokukhobokisa ngokunjalo.
isiphelo
Iziyobisi zinokuchaphazela iinkqubo zomvuzo wengqondo yendalo ukuvelisa umlutha ngeendlela ezintathu kuphela. (1) Imbuyekezo yeziyobisi inokuvula iinkqubo zobuchopho ezifanayo njengembuyekezo enkulu yendalo. Iithiyori zokulutha ezisekwe kwihedonia yeziyobisi eyolisayo okanye ukomelezwa okuqinisekileyo kucingelwa ukuba amachiza asebenza njengembuyekezo yendalo. (2) Imbuyekezo yeziyobisi ezikhobokisayo zinokutshintsha ubungakanani bokukalwa kwamacandelo athile omvuzo, ukuqhekeka kunye nokugqwetha iinkqubo eziqhelekileyo zomvuzo ukubangela isinyanzelo sokuziphatha. Iithiyori zokulutha ezisekwe ekukhuthazeni ukuqina kwenkuthazo ziphakamisa ukuba iziyobisi zikhuthaze i-mesocorticolimbic substrates yenkuthazo, ukwahlula umvuzo wendalo ngokuqinisa "ukufuna" ngokungafaniyo kubangele ukuziphatha okunyanzelekileyo kokuthatha iziyobisi (uRobinson noBerridge, i-2000; uHyman noMalenka, i-2001). Iithiyori zokulutha ezisekelwe kubudlelwane bexesha elide okanye utshintsho kwiinkqubo zokufunda ziphakamisa imikhwa ye-SR yokuthatha iziyobisi ngokungaqhelekanga (O'Brien et al., 1992; Di Chiara, 1998; Robbins and Everitt, 1999; Berke and Hyman, 2000; Everitt et al., 2001). (3) Iziyobisi ezikhobokisayo zinokubangela iinkqubo ezintsha zobuchopho, ezinje ngokurhoxa, ezinokudlala indima enkulu yenkqubo yeqela elichasayo yokulutha kunemivuzo eqhelekileyo (uSolomon noCorbit, 1974; Koob noLe Moal, 2001).
Ezi zinto zintathu zinokwenzeka ziphelele kodwa azihlukani. Izibakala ezininzi ezibangela umdla ziye zafunyanwa ezikhanyisa unxibelelwano lwabo. Izifundo zexesha elizayo ziya kucacisa ngakumbi indlela amachiza asebenzisana ngayo neenkqubo zokuvuza kwengqondo ukuvelisa inkuthazo enyanzelekileyo kunye nokubuyela umva okubonisa ukuba likhoboka.
Imihlathi
• Lo msebenzi uxhaswe yiGranti DA09311, DA04788, kunye neDA13780 evela kwiZiko leSizwe lokuSetyenziswa gwenxa kweZiyobisi (AEK) kunye ne-IBN 0091611 evela kwiNational Science Foundation (KCB). Siyabulela uTerry Robinson, uSheila Reynolds, uMatthew Andrzejewski, noSusana Peciña ngeengcebiso eziluncedo kulo mbhalo-ngqangi.
• Imbalelwano kufuneka ithunyelwe ku-AE Kelley, kwiSebe lezeNgqondo, kwiYunivesithi yaseWisconsin–Madison Medical School, 6001 Research Park Boulevard, Madison, WI 53719. I-imeyile:[imeyile ikhuselwe].
• Ilungelo lokushicilela © 2002 Umbutho weNeuroscience
IZALATHISO
1. ↵
1. Aosaki T,
2. Graybiel AM,
3. UKimura M
(1994) Impembelelo yenkqubo ye-nigrostriatal dopamine ekufumaneni iimpendulo ze-neural kwi-striatum yokuziphatha iinkawu. Inzululwazi 265:412–415 .
I-Abstract / Umbhalo opheleleyo
2. ↵
1. Baldwin AE,
2. Holahan MR,
3. Sadeghian K,
4. Kelley AE
(2000) Iplastiki exhomekeke kwi-N-methy-d-aspartate ye-receptor ngaphakathi kwenethiwekhi ye-corticostriatal esasazwayo ilamla ukufunda kwezixhobo ezinomdla. I-Behav Neurosci 114: 1-15.
3. ↵
1. Baldwin AE,
2. Sadeghian K,
3. Holahan MR,
4. Kelley AE
(2002a) Ukufundwa kwesixhobo sokusebenza kuchaphazeleka kuthintelo lwe-cAMP-exhomekeke kwiprotein kinase ngaphakathi kwi-nucleus accumbens. I-Neurobiol Funda iMem 77: 44-62.
I-CrossRefMedline
4. ↵
1. Baldwin AE,
2. Sadeghian K,
3. Kelley AE
(2002b) Ukufunda ngezixhobo ezikhangayo kufuna ukuba kusetyenziswe i-NMDA kunye nezamkeli ze-DA D1 ngaphakathi kwe-medial prefrontal cortex. J Neurosci 22: 1073-1071.
5. ↵
1. UBaxter MG,
2. UPaka A,
3. Lindner CC,
4. Izquierdo AD,
5. Murray EA
(2000) Ukulawulwa kokukhethwa kweempendulo ngexabiso lokuqinisa kufuna ukusebenzisana kwe-amygdala kunye ne-orbital prefrontal cortex. J Neurosci 20: 4311-4319 .
I-Abstract / Umbhalo opheleleyo
6. ↵
1. Becerra L,
2. Breiter HC,
3. Isilumko R,
4. Gonzalez RG,
5. Borsook D
(2001) Ukuvuza i-neural circuitry activation ngokuvuselela i-neural eyingozi. Neuron 32:927–946 .
I-CrossRefMedline
7. ↵
1. UBerke JD,
2. UHyman SE
(2000) Umlutha, i-dopamine, kunye neendlela zememori zeemolekyuli. I-Neuron 25: 515-532.
I-CrossRefMedline
8. ↵
1. Berridge KC
(2000) Ukulinganisa impembelelo ye-hedonic kwizilwanyana nakwiintsana: i-microstructure ye-affective taste reactivity pattern. I-Neurosci Biobehav Rev 24: 173-198.
I-CrossRefMedline
9. ↵
1. Berridge KC,
2. URobinson TE
(1998) Yintoni indima ye-dopamine emvuzweni: impembelelo ye-hedonic, ukufunda ngomvuzo, okanye ukunyaniseka kwenkuthazo? Res Brain Res 28:309–369.
I-CrossRefMedline
10. ↵
I-Coss RG, i-Owings DH (1989) iRattler fighters. UNat Hist 30–35.
11. ↵
1. Abazala MS,
2. Salamone JD
(1996) Ukubandakanyeka kwe-ventrolateral striatal dopamine ekuqalisweni kwentshukumo kunye nokwenziwa: i-microdialysis kunye nophando lokuziphatha. I-Neuroscience 70: 849-859.
I-CrossRefMedline
12. ↵
1. Das S,
2. UGrunert M,
3. UWilliams L,
4. UVincent SR
(1997) I-NMDA kunye ne-D1 i-receptors ilawula i-phosphorylation ye-CREB kunye nokungeniswa kwe-c-fos kwi-neurons ye-striatal kwinkcubeko yokuqala. Isinapse 25:227–233 .
I-CrossRefMedline
13. ↵
1. UDi Chiara G
(1998) I-hypothesis yokufunda ekhuthazayo yendima ye-mesolimbic dopamine ekusetyenzisweni kweziyobisi okunyanzelekileyo. J Psychopharmacol 12:54–67 .
14. ↵
1. Ettenberg A,
2. Geist TD
(1993) Umahluko womgangatho kunye nobungakanani kwindlela yokuziphatha esebenzayo yeempuku ezisebenzela i-cocaine kunye ne-heroin yokuqinisa. I-Pharmacol Biochem Behav 44: 191-198.
I-CrossRefMedline
15. ↵
1. Everitt BJ,
2. UKhadinali RN,
3. Iholo J,
4. Parkinson JA,
5. Robbins TR
(2000) Ukubandakanyeka okungafaniyo kwe-amygdala subsystems kwi-appetitive conditioning kunye neziyobisi. in The amygdala: uhlalutyo olusebenzayo, ed Aggleton JP (Oxford UP, Oxford), pp 353-390.
16. ↵
1. Everitt BJ,
2. UDickinson A,
3. Robbins TW
(2001) Isiseko se-neuropsychological sokuziphatha okukhobokisayo. ISityhi. 36:129–138.
I-CrossRefMedline
17. ↵
1. Floresco SB,
2. Blaha CD,
3. Yang CR,
4. Phillips AG
(2001a) I-Dopamine D1 kunye ne-NMDA i-receptors mediate potentiation of basolateral amygdala-evoked firing of NAc neurons. J Neurosci 21: 6370-6376.
I-Abstract / Umbhalo opheleleyo
18. ↵
1. Floresco SB,
2. Blaha CD,
3. Yang CR,
4. Phillips AG
(2001b) Ukumodareyithwa kwe-hippocampal kunye nomsebenzi okhutshwe yi-amygdalar we-nucleus accumbens neurons nge-dopamine: iindlela zeselula zokukhetha igalelo. J Neurosci 21: 2851-2860.
I-Abstract / Umbhalo opheleleyo
19. ↵
1. Iglasi yeMJ,
2. UBillington CJ,
3. Levine AS
(1999) I-Opioids kunye nokutya kokutya: ukuhanjiswa kweendlela ze-neural ezisebenzayo? I-Neuropeptides 33: 360-368.
I-CrossRefMedline
20. ↵
1. Yiya ku-Y,
2. O'Donnell P
(2001) I-synchrony yenethiwekhi kwi-nucleus accumbens kwi-vivo. J Neurosci 21: 4498-4504.
I-Abstract / Umbhalo opheleleyo
21. ↵
1. Grey JA,
2. Kumari V,
3. ULawrence N,
4. I-AMJ eselula
(1999) Imisebenzi ye-dopamine innervation ye-nucleus accumbens. I-Psychobiology 27: 225-235 .
22. ↵
1. Igrill HJ,
2. UNorgren R
(1978) Uvavanyo lokusebenzisa incasa. I. Iimpendulo zeMimetic kwi-gustatory stimuli kwiigundane eziqhelekileyo ze-neurologically. I-Brain Res 143: 263-279.
I-CrossRefMedline
23. ↵
1. UGurden H,
2. Takita M,
3. Jay TM
Indima ebalulekileyo ye-D1 kodwa kungekhona i-D2 i-receptors kwi-NMDA exhomekeke kwi-receptor-dependent potentiation kwi-hippocampal-prefrontal cortex synapses kwi-vivo.J Neurosci202000RC106 (1-5).
24. ↵
1. Horvitz JC
(2000) Iimpendulo ze-Mesolimbocortical kunye ne-nigrostriatal dopamine kwiziganeko ezingenamvuzo. I-Neuroscience 96: 651-656.
I-CrossRefMedline
25. ↵
1. UHyman SE,
2. UMalenka RC
(2001) Umlutha kunye nengqondo: i-neurobiology yokunyanzeliswa kunye nokuzingisa kwayo. I-Nat Rev Neurosci 2: 695-703.
I-CrossRefMedline
26. ↵
1. Ikemoto S,
2. UPanksepp J
(1999) Indima ye-nucleus accumbens dopamine kwindlela yokuziphatha ekhuthazayo: ukutolika okuhlanganisayo kunye nereferensi ekhethekileyo yokufuna umvuzo. ISityhi. 31:6–41.
I-CrossRefMedline
27. ↵
1. UJackson ME,
2. UMoghaddam B
(2001) Ummiselo we-Amygdala we-nucleus accumbens imveliso ye-dopamine ilawulwa yi-prefrontal cortex. J Neurosci 21: 676-681.
I-Abstract / Umbhalo opheleleyo
28. ↵
1. Jog MS,
2. Kubota Y,
3. UConnolly CI,
4. Hillegaart V,
5. Graybiel AM
(1999) Ukwakha ukubonakaliswa kwe-neural yemikhuba. Inzululwazi 286:1745–1749.
I-Abstract / Umbhalo opheleleyo
29. ↵
1. Kalivas PW,
2. UNakamura M
(1999) Iinkqubo zeNeural zokuvula indlela yokuziphatha kunye nomvuzo. Curr Opin Neurobiol 9: 223-227.
I-CrossRefMedline
30. ↵
1. Kelley AE
(1999) Imisebenzi yokudibanisa i-Neural ye-nucleus accumbens subregions ngokumalunga nokukhuthaza kunye nokufunda. I-Psychobiology 27: 198-213.
31. ↵
I-Kelley AE, i-Bakshi V, i-Haber SN, i-Steininger TL, i-Will MJ, i-Zhang M (2002) Ukuguqulwa kwe-Opioid ye-taste hedonics ngaphakathi kwe-ventral striatum. Physiol Behav, kushicilelo.
32. ↵
1. Konradi C,
2. Leveque JC,
3. UHyman SE
(1996) I-Amphetamine kunye ne-dopamine-induced-induced gene expression kwangoko kwi-neuron ye-striatal ixhomekeke kwi-postsynaptic NMDA receptors kunye ne-calcium. J Neurosci 16: 4231-4239 .
I-Abstract / Umbhalo opheleleyo
33. ↵
1. Koob GF,
2. Le Moal M
(2001) Umlutha weziyobisi, ukungasebenzi kakuhle komvuzo, kunye ne-allostasis. I-Neuropsychopharmacology 24: 97-129.
I-CrossRefMedline
34. ↵
1. Legault M,
2. Ubulumko RA
(2001) Ukuphakama kwe-nucleus accumbens dopamine entsha: ukuxhomekeka kwi-impulse flow esuka kwi-ventral subiculum kunye ne-glutamatergic neurotransmission kwindawo ye-ventral tegmental. I-Eur J Neurosci 13: 819-828.
I-CrossRefMedline
35. ↵
1. Mulder AB,
2. Hodenpijl MG,
3. Lopes da Silva FH
(1998) I-Electrophysiology ye-hippocampal kunye ne-amygdaloid projection to the nucleus accumbens of the rat: convergence, segregation, and interaction of inputs. J Neurosci 18: 5095-5102.
I-Abstract / Umbhalo opheleleyo
36. ↵
1. O'Brien CP,
2. Childress AR,
3. McLellan T,
4. U-Ehrman R
(1992) Imodeli yokufunda yokulutha. kwiAddictive states, eds O'Brien CP, Jaffe J (Raven, New York), pp 157–177.
37. ↵
1. O'Donnell P,
2. Ubabalo AA
(1995) Ukusebenzisana kwe-Synaptic phakathi kwee-excitatory afferents kwi-NAc neurons: i-hippocampal gating ye-prefrontal cortical input. J Neurosci 15: 3622-3639 .
Abstract
38. ↵
1. Amatyala DH,
2. Morton ES
(1998) Unxibelelwano ngelizwi lezilwanyana: indlela entsha. (eCambridge UP, eNew York).
39. ↵
1. Packard MG,
2. I-NM emhlophe
(1990) Izilonda ze-caudate nucleus ngokukhetha ziphazamisa ukufunyanwa kwe "reference memory" kwi-radial maze. I-Behav Neural Biol 53: 39-50.
I-CrossRefMedline
40. ↵
1. Parkinson JA,
2. Robbins TW,
3. Everitt BJ
(1999) Izilonda ezikhethiweyo ze-excitotoxic ze-nucleus accumbens core kunye neqokobhe ngokuhlukileyo zichaphazela i-aversive Pavlovian conditioning to discrete and contextual cues. I-Psychobiology 27: 256-266 .
41. ↵
1. I-Paxinos G,
2. Watson C
(1998) Iatlasi yestereotaxic yobuchopho bempuku. (Ezemfundo, eNew York).
42. ↵
1. Peciña S,
2. Berridge KC
(2000) Indawo yokutya ye-opioid kwi-nucleus accumbens iqokobhe idibanisa ukutya kunye ne-hedonic "ukuthanda": imephu esekwe kwi-microinjection Fos plumes. I-Brain Res 863:71–86.
I-CrossRefMedline
43. ↵
1. Peciña S,
2. Berridge KC,
3. Parker LA
(1997) I-Pimozide ayitshintshi i-palatability: ukwahlukana kwe-anhedonia ukusuka kuxinzelelo lwe-sensorimotor yi-taste reactivity. I-Pharmacol Biochem Behav 58:801–811.
I-CrossRefMedline
44. ↵
1. Petrovich GD,
2. Canteras NS,
3. ISwanson L
(2001) Igalelo le-amygdalar elidityanisiweyo kwiindawo ze-hippocampal kunye neenkqubo zokuziphatha ze-hypothalamic. Res Brain Res Brain Res Res 38:247–289.
I-CrossRefMedline
45. ↵
1. Piazza PV,
2. I-Rouge-Pont F,
3. Deroche V,
4. Maccari S,
5. USimon H,
6. Le Moal M
(1996) I-Glucocorticoids ineempembelelo ezixhomekeke kurhulumente kwi-mesencephalic dopaminergic transmission. Proc Natl Acad Sci USA 93:8716-8720.
I-Abstract / Umbhalo opheleleyo
46. ↵
1. Rada P,
2. Tucci S,
3. UMurzi E,
4. UHernandez L
(1997) I-glutamate ye-extracellular iyanda kwi-hypothalamus esecaleni kwaye iyancipha kwi-nucleus accumbens ngexesha lokutya. I-Brain Res 768: 338-340.
I-CrossRefMedline
47. ↵
1. Rada PV,
2. Maka GP,
3. Hoebel BG
(1998) Ukukhutshwa kwe-Dopamine kwi-nucleus accumbens ngokuziphatha kwe-hypothalamic stimulation-escape. I-Brain Res 782: 228-234.
I-Medline
48. ↵
1. I-Redgrave P,
2. Prescott TJ,
3. UGurney K
(1999) Ngaba impendulo ye-dopamine ye-latency emfutshane imfutshane kakhulu ukuba ibonise impazamo yomvuzo? Iimpawu zeNeurosci 22: 146-151.
I-CrossRefMedline
49. ↵
1. Reynolds SM,
2. Berridge KC
(2001) Uloyiko kunye nokutya kwi-nucleus accumbens igobolondo: ukwahlukaniswa kwe-rostrocaudal ye-GABA-elicited yokuziphatha ngokuzikhusela ngokuchasene nokuziphatha kokutya. J Neurosci 21: 3261-3270.
I-Abstract / Umbhalo opheleleyo
50. ↵
1. Robbins TW,
2. Everitt BJ
(1999) Ukulutha kweziyobisi: imikhwa emibi yongeza. Indalo 398: 567-570.
I-CrossRefMedline
51. ↵
1. URobinson TE,
2. Berridge KC
(1993) Isiseko se-neural sokunqwenela iziyobisi: ithiyori ye-incentive-sensitization ye-addiction. ISityhi. 18:247–291.
I-CrossRefMedline
52. ↵
1. URobinson TE,
2. Berridge KC
(2000) Isayikholoji kunye neurobiology yokulutha: umbono wokukhuthaza. Ikhoboka 95:91–117 .
CrossRef
53. ↵
1. Imiqulu ET
(1999) Ingqondo kunye novakalelo. (Oxford UP, Oxford).
54. ↵
1. Salamone JD
(1994) Ukubandakanyeka kwe-nucleus accumbens i-dopamine kwi-appetitive kunye ne-aversive motivation. I-Behav Brain Res 61:117–133.
I-CrossRefMedline
55. ↵
1. Schoenbaum G,
2. Chiba AA,
3. UGallagher M
(1999) I-Neural encoding kwi-cortex ye-orbitofrontal kunye ne-basolateral amygdala ngexesha lokufunda ucalucalulo lwe-olfactory. J Neurosci 19: 1876-1884.
I-Abstract / Umbhalo opheleleyo
56. ↵
1. USchultz W
(2000) Iimpawu zomvuzo ezininzi engqondweni. I-Nat Rev Neurosci 1: 199-207.
I-Medline
57. ↵
1. Abaselwandle uJK,
2. Durstewitz D,
3. UChristie BR,
4. Stevens CF,
5. Sejnowski TJ
(2001) I-DA D1 / D5 i-receptor modulation ye-excitatory synaptic inputs to layer V prefrontal cortex neurons. Proc Natl Acad Sci USA 98:301–306.
I-Abstract / Umbhalo opheleleyo
58. ↵
1. Smith-Roe SL,
2. Kelley AE
(2000) Ukusebenza ngengozi kwe-NMDA kunye ne-dopamine D1 receptors ngaphakathi kwe-nucleus accumbens core iyafuneka ekufundeni isixhobo sokudlala. J Neurosci 20: 7737-7742 .
I-Abstract / Umbhalo opheleleyo
59. ↵
1. USolomon RL,
2. Corbit JD
(1974) Ithiyori yenkqubo echasayo yenkuthazo: I. I-Temporal dynamics of impact. ISityhi 81:119–145 .
I-CrossRefMedline
60. ↵
1. Steiner JE,
2. Iglasi D,
3. Hawilo ME,
4. Berridge KC
(2001) Ukuthelekisa ukubonakaliswa kwempembelelo ye-hedonic: iimpendulo ezithintekayo kwincasa yeentsana zabantu kunye nezinye iiprimates. I-Neurosci Biobehav Rev 25: 53-74.
I-CrossRefMedline
61. ↵
1. UStewart J,
2. Ubulumko RA
(1992) Ukubuyiselwa kwemikhwa yokulawula i-heroin: i-morphine ikhuthaza kunye ne-naltrexone iyakudimaza ukusabela okuhlaziyiweyo emva kokuphela. I-Psychopharmacology 108:79-84.
I-CrossRefMedline
62. ↵
1. Stratford TR,
2. Kelley AE
(1999) Ubungqina bobudlelwane obusebenzayo phakathi kwegobolondo le-NAc kunye ne-hypothalamus esecaleni ethobela ulawulo lokuziphatha kokutyisa. J Neurosci 19: 11040-11048.
I-Abstract / Umbhalo opheleleyo
63. ↵
1. ISwanson LW
(2000) Ukulawulwa kwe-Cerebral hemisphere yokuziphatha okukhuthazwayo. I-Brain Res 886: 113-164.
I-CrossRefMedline
64. ↵
1. Treit D,
2. IPinel JP,
3. IFibiger HC
(1981) Ukungcwaba okukhuselekileyo okusemgangathweni: i-paradigm entsha yokufunda i-agent anxiolytic. I-Pharmacol Biochem Behav 15: 619-626.
I-CrossRefMedline
65. ↵
1. Uslaner J,
2. Badiani A,
3. Norton CS,
4. Usuku HE,
5. Watson SJ,
6. Akil H,
7. URobinson TE
(2001) I-Amphetamine kunye ne-cocaine zikhuthaza iipatheni ezahlukeneyo ze-c-fos mRNA intetho kwi-striatum kunye ne-subthalamic nucleus ngokuxhomekeke kwimeko yokusingqongileyo. I-Eur J Neurosci 13: 106-113 .
66. ↵
1. IVolkow ND,
2. Wang GJ,
3. Fowler JS,
4. Logan J,
5. Gatley SJ,
6. Wong C,
7. Hitzemann R,
8. I-Pappas NR
(1999) Ukuqinisa iziphumo ze-psychostimulants ebantwini zinxulunyaniswa nokunyuka kwe-dopamine yengqondo kunye nokuhlala kwe-D-2 receptors. J Pharmacol Exp Ther 291:409–415.
I-Abstract / Umbhalo opheleleyo
67. ↵
1. Wang J,
2. O'Donnell P
(2001) D (1) i-dopamine receptors zenza ukwanda kwe-NMDA-mediated excitability kuluhlu lwe-V prefrontal cortical pyramidal neurons. Cereb Cortex 11:452–462.
I-Abstract / Umbhalo opheleleyo
68. ↵
1. I-NM emhlophe
(1989) I-hypothesis esebenzayo malunga ne-matrix yokubetha kunye neepatches: ulamlo lwenkumbulo ye-SR kunye nomvuzo. Ubomi Sci 45: 1943-1957.
I-CrossRefMedline
69. ↵
1. Ubulumko RA
(1985) Ingqikelelo ye-anhedonia: UMarko III. Behav Brain Sci 8:178–186.
70. ↵
1. UWyvell CL,
2. Berridge KC
(2000) I-Intra-nucleus accumbens amphetamine yonyusa umgangatho wenkuthazo omiselweyo womvuzo we-sucrose: ukongezwa komvuzo “ukufuna” ngaphandle “kokuthanda” okuphuculweyo okanye ukuqinisa impendulo. J Neurosci 20: 8122-8130.
I-Abstract / Umbhalo opheleleyo
71. ↵
1. Zahm DS
(2000) Umbono odibeneyo we-neuroanatomical kwezinye ii-substrates ezingaphantsi kwe-adaptive yokuphendula ngokugxininisa kwi-nucleus accumbens. I-Neurosci Biobehav Rev 24: 85-105.
I-CrossRefMedline
72. ↵
1. UZhang M,
2. Kelley AE
(2000) Ukutya okuphuculweyo kokutya okunamafutha amaninzi emva kokuvuselela i-mu-opioid ye-striatal: imephu ye-microinjection kunye ne-fos expression. I-Neuroscience 99: 267-277.
I-CrossRefMedline
Amaqaku acacisa eli nqaku
• Ukuqiniswa kokutya, ukuthathwa kwamandla, kunye nokhetho lwe-macronutrient I-American Journal of Clinical Nutrition, 1 July 2011, 94(1): 12-18
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Imbuyekezo yokutya, i-hyperphagia, kunye nokutyeba kakhulu i-American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 1 Juni 2011, 300(6):R1266-R1277
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Dopaminergic modulation yenkqubo yomvuzo womntu: i-placebo-controlled dopamine depletion study fMRI Journal of Psychopharmacology, 1 April 2011, 25 (4): 538-549
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Sucrose self-administration kunye nokusebenza kwe-CNS kwirat American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 1 April 2011, 300(4):R876-R884
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukukhethwa komngcipheko olandela ukusetyenziswa kotywala kolutsha kunxulunyaniswa nokufakwa kweekhowudi ezonakeleyo kodwa hayi imbuyekezo nge-mesolimbic dopamine PNAS, 29 Matshi 2011, 108(13):5466-5471
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Iziphumo zesicatshulwa seRhodiola rosea L. ekufumaneni nasekuboniseni ukunyamezela imorphine kunye nokuxhomekeka kwiimpuku Ijenali yePsychopharmacology, 1 Matshi 2011, 25(3):411-420
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Izitayile zokuhlangabezana kunye nokuguquguquka kokuziphatha: ukuya kwiindlela ezisisiseko IiNtengiselwano zefilosofi yeRoyal Society B: iBiological Sciences, 27 Disemba 2010, 365(1560):4021-4028
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukulawulwa kwe-Nucleus Accumbens Activity yi-Hypothalamic Neuropeptide Melanin-Concentrating Hormone Journal of Neuroscience, 16 Juni 2010, 30 (24): 8263-8273
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Extracellular Signal-Regulated Kinase-2 ngaphakathi kwi-Ventral Tegmental Area ilawula iiMpendulo zeStress Journal of Neuroscience, 2 Juni 2010, 30 (22): 7652-7663
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukukhanuka Ngelixa Uzithiyile: IParallel Counterdriving of Wanting and Liking Psychological Science, 1 January 2010, 21(1):118-125
o Isiqendu esipheleleyo (PDF)
• IiMveliso zeGhrelin Gene kunye nokuLawulwa kokuTya kunye neGut Motility Pharmacological Reviews, 1 December 2009, 61(4):430-481
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukuthelekiswa kwe-Combined Bupropion kunye ne-Naltrexone Therapy for Obesity kunye ne-Monotherapy kunye ne-Placebo Journal ye-Clinical Endocrinology & Metabolism, 1 December 2009, 94 (12): 4898-4906
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Iinguqu zeDiurnal kuMvuzo weNdalo kunye neziyobisi, i-Mesolimbic Tyrosine Hydroxylase, kunye neClock Gene Expression kwiMale Rat Journal yeBiological Rhythms, 1 Disemba 2009, 24(6):465-476
o Isishwankathelo
o Isiqendu esipheleleyo (PDF)
• UkuLungiswa koMvuzo yiNkqubo ye-Opioid kwi-Brain Physiological Reviews, i-1 ka-Oktobha 2009, i-89 (4): 1379-1412
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-ghrelin-secreting cells yesisu njengewotshi ye-circadian ene-entrainable yokutya PNAS, 11 Agasti 2009, 106(32): 13582-13587
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• IMimandla yeBrain eNxulumene nokuSetyenziswa kweSixhobo kunye noLwazi lokuSebenza lubonakalisa i-Nicotine Dependence Journal of Neuroscience, 15 April 2009, 29(15): 4922-4929
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Iziphumo zecocaine kumjuxuzo wenyosi yobusi Ijenali ye-Experimental Biology, 15 January 2009, 212(2):163-168
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-insulin, i-leptin, kunye nomvuzo wokutya: ukuhlaziywa 2008 American Journal of Physiology – Regulatory, Integrative and Comprerative Physiology, 1 January 2009, 296(1):R9-R19
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Impendulo ekumgangatho ongemva-ngasemva kwi-Otx2 ilawula ukwanda kunye nokwahlulahlulwa kwe-dopaminergic progenitors kuphuhliso lwe-ventral mesencephalon, 15 Oktobha 2008, 135 (20): 3459-3470
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• UPhando oluKhethekileyo loThutho lweDopamine ngaphakathi kwe-Nucleus Accumbens Shell yiCocaine Ibalelwa kuKunyuka okuNgqo kwi-Phasic Dopamine Release Events Journal of Neuroscience, 27 Agasti 2008, 28(35):8821-8831
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukutyhila isiphithiphithi sokuvuzwa kweziyobisi kwindaleko yoluntu Iinkqubo zeRoyal Society B: iBiological Sciences, 7 Juni 2008, 275(1640):1231-1241
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Coregulation, Dysregulation, Self-Regulation: Uhlahlelo oluDityanisiweyo kunye ne-Empirical Agenda yokuQonda ukuqhotyoshelwa kwabantu abadala, ukwahlukana, ilahleko, kunye nokuBuyisa koBumo kunye noPhononongo lwePsychology yeNtlalo, 1 Meyi 2008, 12(2): 141-167
o Isishwankathelo
o Isiqendu esipheleleyo (PDF)
• I-Cdk5 Modulates Cocaine Reward, Motivation, and Striatal Neuron Excitability Journal of Neuroscience, 21 Novemba 2007, 27 (47): 12967-12976
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Peptide YY3-36 iyancipha ukuBuyiselwa kokuTyelwa kweFat-Fat ngexesha lokuTya kwi-Rat Relapse Model Journal ye-Neuroscience, i-24 ka-Oktobha 2007, i-27 (43): 11522-11532
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukubonakaliswa kwe-Orexin kwi-Ventral Tegmental Area ifuneka kwi-High-Fat Appetite eveliswa yi-Opioid Stimulation ye-Nucleus Accumbens Journal of Neuroscience, 10 October 2007, 27(41): 11075-11082
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-vasopressin elawulwa kumbindi ikhuthaza iimpuku kwi-amphetamine nokusela i-hypertonic NaCl American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 1 Septemba 2007, 293(3):R1452-R1458
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukunciphisa iVesicular Somatodendritic Dopamine Stores kwiLeptin-Deficient Mice Journal of Neuroscience, 27 June 2007, 27(26): 7021-7027
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukusuka kwimpazamo yokuxela kwangaphambili ukuya kwi-psychosis: i-ketamine njengemodeli ye-pharmacological ye-delusions Journal of Psychopharmacology, 1 May 2007, 21(3): 238-252
o Isishwankathelo
o Isiqendu esipheleleyo (PDF)
• UFikelelo lweMihla ngeMihla oluNcinciweyo kwiSiselo esiSwiti sithobisa iHypothalamic-Pituitary-Adrenocortical Axis Stress Responses Endocrinology, 1 April 2007, 148(4):1823-1834
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Unxibelelwano lwe-Intraspecific ngokusetyenziswa kweMiqondiso yeMichiza kwiiMpawu eziBhinqileyo: Ukuqinisa iiMpahla zeMchiza yeePheromones zeSidoda eziNgaguqukiyo, 1 February 2007, 32(2):139-148
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ilahleko eqhubekayo yeeNeurons zeDopaminergic kwi-Ventral Midbrain ye-Adult Mice Heterozygote ye-Engrailed1 Journal of Neuroscience, 31 January 2007, 27(5): 1063-1071
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Umlutha: Isifo sokuFunda kunye nokuGxininisa kwiMemori, 1 January 2007, 5(2): 220-228
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Iisekethe ze-Hypothalamic neural ezilawula ukuphendula kukamama kwiintsana. Uphononongo lwe-Neuroscience yokuziphatha kunye neNgcaciso, i-1 kaDisemba 2006, i-5 (4): 163-190
o Isishwankathelo
o Isiqendu esipheleleyo (PDF)
• INeuroscience yolonwabo. Gxininisa kwi "Ventral Pallidum Firing Codes Hedonic Reward: Xa iTaste embi ijika ilungile" I-Journal ye-Neurophysiology, i-1 kaNovemba 2006, i-96 (5): 2175-2176
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukuziphatha kokutyisa kwe-Aplysia: Inkqubo eyimodeli yokuthelekisa iindlela zeselula ze-classical kunye ne-operating conditioning Learning & Memory, 1 Novemba 2006, 13(6): 669-680
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Uthintelo lwesodium yangaphambi kokubeleka nasemva kokubeleka ivuselela impuku yabantu abadala kwi-amphetamines American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 1 October 2006, 291(4):R1192-R1199
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Bidirectional Dopaminergic Modulation of Excitatory Synaptic Transmission in Orexin Neurons Journal of Neuroscience, 27 Septemba 2006, 26 (39): 10043-10050
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ulawulo olubhaliweyo lophuhliso lwe-midbrain dopaminergic neuron Development, 15 Septemba 2006, 133(18):3499-3506
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• {I-Delta} i-FosB kwi-Nucleus Accumbens ilawula i-Food-Reinforced Instrumental Behaviour and Motivation Journal of Neuroscience, 6 Septemba 2006, 26 (36): 9196-9204
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Umahluko ngamnye kumvuzo wokuqhuba uqikelela iimpendulo zemithambo-luvo kwimifanekiso yokutya. Ijenali ye-Neuroscience, i-10 ngoMeyi 2006, i-26 (19): 5160-5166
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Galanin kunye ne-Galanin-Njenge-Peptide engafaniyo iModulating Neuronal Activities kwiRat Arcuate Nucleus Neurons Journal of Neurophysiology, 1 May 2006, 95 (5): 3228-3234
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Ventral Pallidum kunye nomvuzo we-Hedonic: I-Neurochemical Maps ye-Sucrose "Ukuthanda" kunye ne-Food Intake Journal ye-Neuroscience, i-21 Septemba 2005, i-25 (38): 8637-8649
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Izilonda ze-Subthalamic Nucleus Ziphucula i-Psychomotor-Activating, Incentive Motivational, kunye neNeurobiological Effects yeCocaine Journal of Neuroscience, 14 Septemba 2005, 25(37):8407-8415
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• UKUTYELWA KWE-ETHANOL NGOKUZITHANDELA KUYONGEZA AMANQANABA ABANGAPHEZULU KWE-ACETYLCHOLINE KWINDAWO YE-VENTRAL TEGMENTAL KWI-RAT Alcohol and Alcoholism, 1 Septemba 2005, 40(5):349-358
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Dopamine Receptor Stimulation Modulates AMPA Receptor Synaptic Insertion kwi-Prefrontal Cortex Neurons Journal of Neuroscience, 10 Agasti 2005, 25 (32): 7342-7351
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Umlutha: Isifo sokuFunda kunye neMemori i-American Journal of Psychiatry, 1 Agasti 2005, 162 (8): 1414-1422
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• IMIPHUMELA YE-NALTREXONE KWI-ETHANOL-EYEnziwa UTSHINTSHO KWI-RAT CENTRAL DOPAMINERGIC SYSTEM Utywala kunye noTywala, 1 Julayi 2005, 40(4): 297-301
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Neurobiology yeempuku eziKhethelwe uMsebenzi oPhezulu wokuZithandela woKuqhutywa kwevili lokuDityaniswa nokuThetha iBhayoloji, ngomhla woku-1 kuJuni 2005, 45(3):438-455
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Metabotropic Glutamate Receptor mGlu5 nguMlamli we-Appetite kunye neBalance yaMandla kwiiRats kunye neMice Journal ye-Pharmacology kunye noNyango loMvavanyo, 1 April 2005, 313 (1): 395-402
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• IHypothalamic Neuropeptide Melanin-Concentrating Hormone Act in the Nucleus Accumbens to Modulate Feeding Behaviour and Forced-Swim Performance Journal of Neuroscience, 16 March 2005, 25(11):2933-2940
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Mesolimbic Dopamine Super-Sensitivity kwi-Melanin-Concentrating Hormone-1 Receptor-Deficient Mice Journal of Neuroscience, 26 January 2005, 25 (4): 914-922
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukungcamla iimpendulo kwizigulane ezine-Parkinson's disease Journal of Neurology, Neurosurgery & Psychiatry, 1 January 2005, 76(1):40-46
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-NEuroscience: I-Addicted Rats Science, 13 Agasti 2004, 305(5686):951-953
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Utywala Busebenzisa i-Sucrose-Responsive Gustatory Neural Pathway Journal of Neurophysiology, 1 Julayi 2004, 92 (1): 536-544
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Kinase ye-1/2 ye-Phosphorylation eGciniweyo ye-Extracellular Signal kwi-Neonate 6-Hydroxydopamine-Lesioned Rats emva kokuPhindwa kwe-D1-Dopamine Receptor Agonist Administration: Iimpembelelo ze-NMDA Receptor Involvement Journal of Neuroscience, 30 Juni 2004-24: 26 (5863)
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Nicotinic Receptor Modulation ye-Dopamine Transporter Function kwi-Rat Striatum kunye ne-Medial Prefrontal Cortex Journal ye-Pharmacology kunye ne-Experimental Therapeutics, 1 kaJanuwari 2004, 308(1): 367-377
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Iimpembelelo ze-opioid antagonist naltrexone ekutyisweni okubangelwa yi-DAMGO kwindawo ye-ventral tegmental kunye ne-nucleus accumbens kwingingqi yeqokobhe kwirat American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 1 Novemba 2003, 285 (R5-999) I-R1004
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Hyperdopaminergic Mutant Iigundane zineeMpawu eziPhakamileyo "Ezifunayo" Kodwa "Azithandi" kwiJenali yemivuzo eSweet ye-Neuroscience, i-15 ka-Oktobha 2003, i-23 (28): 9395-9402
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• I-Phospholipase C{gamma} kwiMimandla eMisiweyo yoMmandla we-Ventral Tegmental ngokungafaniyo iModulates iMood-Related Behaviors Journal of Neuroscience, 20 Agasti 2003, 23(20):7569-7576
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukunyuswa kwe-ventral striatal monoaminergic innervation kwiTourette syndrome Neurology, 12 Agasti 2003, 61(3):310-315
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Indima ebalulekileyo ye-Nucleus Accumbens Dopamine kwi-Partner-Preference Formation kwi-Male Prairie Voles Journal of Neuroscience, 15 April 2003, 23 (8): 3483-3490
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Imiqondiso ye-adiposity kunye nomvuzo wokutya: ukwandisa iindima ze-CNS ze-insulin kunye ne-leptin American Journal of Physiology – Regulatory, Integrative and Comprerative Physiology, 1 April 2003, 284(4):R882-R892
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Ukurhoxiswa kwi-Repeated Cocaine Alters Dopamine Transporter Protein Turnover kwiRat Striatum Journal of Pharmacology and Experimental Therapeutics, 1 January 2003, 304(1):15-21
o Isishwankathelo
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
• Indlela yokuziphatha / yeeNkqubo kwi-Neuroscience ye-Drug Addiction Journal ye-Neuroscience, i-1 Meyi 2002, i-22 (9): 3303-3305
o Isicatshulwa esipheleleyo
o Isiqendu esipheleleyo (PDF)
;