Imivuzo yemvelo, i-Neuroplasticity, kunye ne-Ad-drug Addictions (i-2011)

Neuropharmacology. I-2011 ngoDisemba; 61(7): 1109-1122. Ishicilelwe kwi-intanethi 2011 April 1. ikhonkco:  10.1016 / j.neuropharm.2011.03.010

PMCID: PMC3139704  NIHMSID: NIHMS287046
Inguqulelo yokugqibela yomhleli yeli nqaku iyafumaneka apha Neuropharmacology
Bona amanye amanqaku ku-PMC Wisdom nqaku epapashwe.

Abstract

Tnantsi inqanaba eliphezulu lokugqwesa phakathi kwemimandla yobuchopho ebandakanyeka ekusebenzeni ngemivuzo yendalo kunye neziyobisi zokuxhatshazwa. "Iziyobisi" ezingezo iziyobisi "okanye" ekuziphatheni "zibhaliwe eklinikhi, kwaye i-pathologies ibandakanya imisebenzi enyanzelekileyo enje ngokuthenga, ukutya, ukuzilolonga, ukuziphatha ngokwesondo kunye nokungcakaza..

Njengokusetyenziswa kweziyobisi, iziyobisi ezingekho iziyobisi zibonakalisa iimpawu kubandakanya inkanuko, ulawulo olungalunganga kwindlela yokuziphatha, ukunyamezelana, ukurhoxa kunye nokuphakama okuphezulu kwakhona. Olu tshintsho kwindlela yokuziphatha lucebisa ukuba ubukho beplastiki bunokwenzeka kwimimandla yobuchopho enxulumene nokusetyenziswa kweziyobisi.

Kolu hlaziyo, ndishwankathela idatha ebonisa ukuba ukubonakaliswa kwimivuzo engeyiyo iziyobisi kunokutshintsha ubukho beplastiki kwimimandla yengqondo echaphazeleka ziziyobisi zokuxhatshazwa. Uphando lubonisa ukuba kukho ukufana okukhoyo phakathi kwe-neuroplasticity ebangelwa yimbuyekezo yendalo kunye neziyobisi kwaye, kuxhomekeke kumvuzo, ukubhengeza okuphindaphindiweyo kwimivuzo yendalo kunokubangela i-neuroplasticity ekhuthaza okanye ichasene nokuziphatha okuchasayo.

Internet: ukufuna izinto ezintsha, iziyobisi, ukukhuthaza, ukuqinisa, isimilo, iplasitiki

1. intshayelelo

Kukho iinkqubo zikamabonwakude ezibalaseleyo ezibonisa abantu abaziphatha ngokunganyanzelekanga ukuba baziphathe ngendlela ezinokuthi zithathwe njengesiqhelo, kodwa zenze ngendlela enefuthe elibi kubomi babo nakwabo kwiintsapho zabo. PAbantu abaphethwe zizinto ezinokuthi zithathwe njengeziyobisi 'ezingezozamachiza' okanye "ngokuziphatha" ziya zisiba bukhali ekliniki, kwaye iimpawu zibandakanya imisebenzi enyanzelekileyo enje ngokuthenga, ukutya, ukuzilolonga, ukuziphatha ngokwesondo, ukungcakaza, kunye nemidlalo yevidiyo. (Holden, 2001; Grant okqhubekayo, 2006a). Ngelixa izifundo zale midlalo kamabonakude zisenokubonakala ngathi zinemeko ezigqithisileyo nezinqabileyo, ezi ntlobo zokuphazamiseka zixhaphakile ngendlela eyoyikisayo. Amanqanaba osungulo eUnited States aqikelelwa kwi-1-2% yongcakazo lwe-pathological (Welte okqhubekayo, 2001), I-5% yokuziphatha ngokwesondo okunyanzelekileyo (I-Schaffer kunye neZimmerman, 1990), I-2.8% yentsholongwane yokutya ngokutya okuneentsholongwane (Hudson okqhubekayo, 2007) kunye ne-5-6% yokuthenga okunyanzelekileyo (Abamnyama, i-2007).

Nangona iDSM-IV iyazamkela ezi ngxaki kunye nezinye eziziphatha “ezingekho mthethweni”, okwangoku azihlukaniswa njengeziyobisi. Oku kungenxa yokuba i-DSM-IV iyaluphepha ugqithiso lwamagama nangona kubhekiswa kwiziyobisi zokuphathwa gadalala, ukhetha amagama athi "ukuxhatshazwa" kunye "nokuxhomekeka". KwiDSM-IV, iziyobisi ezinxulumene nokuziphatha zihlelwe phantsi kwezigaba ezifana "nokuphazamiseka kwento enxulumene neziyobisi", "iingxaki zokutya", kunye "nokuphazamiseka kolawulo olunempembelelo olungachazwanga kwenye indawo" (Holden, 2001; Umkhuhlane, i-2006). Kutshanje, kuye kwakho umkhwa wokucinga ngezi ziyobisi zingalungelanga ukufana nokusetyenziswa gwenxa kweziyobisi kunye nokuxhomekeka (Rogers no Smit, 2000; wang okqhubekayo, 2004b; IVolkow kunye neWise, 2005; Grant okqhubekayo., 2006a; I-petry, i-2006; Teegarden neBale, i-2007; Isishwankathelo, i2010; Grant okqhubekayo, 2010). Ngapha koko, iziyobisi ezingalunganga ziyobisi zilungele inkcazo yeklasi yokulutha kubandakanya ukubandakanyeka ekuziphatheni ngaphandle kwemiphumo emibi kakhulu (Holden, 2001; uHyman okqhubekayo, 2006). Le nto iye yaxatyiswa ziingcali zeengqondo, kwaye kwenziwa izindululo zokuhlaziywa kwe-DSM-5 kubandakanya udidi lweZiyobisi kunye nokuziphatha okuhambelana noko ((APA), 2010). Ngaphakathi kolu luhlu, kuphakanyisiwe icandelo loKuziphatha njengento ethandabuzekayo, eya kubandakanya ukugembula kwengqondo kunye nokubanakho ukuba likhoboka le-intanethi ((APA), 2010; I-O'Brien, 2010; Tao okqhubekayo, 2010).

Njengokuthengisa iziyobisi, iziyobisi ezingekho kweziyobisi zibonisa kwiindlela ezifanayo zengqondo kunye nokuziphatha kubandakanya ukulangazelela, ukulawula okungalunganga kwindlela yokuziphatha, ukunyamezelana, ukurhoxa, kunye neqondo eliphezulu lokuphinda ubuye (Amanqaku, 1990; I-Lejoyeux okqhubekayo, 2000; IZiko leLizwe leSizwe ngokuSetyenziswa gwenxa kweziyobisi (NIDA) okqhubekayo, 2002; Umkhuhlane, i-2006). Ukufana phakathi kwamachiza kunye nembuyekezo engeyiyo yeziyobisi kunokubonwa ngokwasemzimbeni. Izifundo ezisebenzayo ze-neuroimaging ebantwini zibonise ukuba ukungcakaza (Ibreaker okqhubekayo, 2001), Ivenkile (Knutson okqhubekayo, 2007),Komisaruk okqhubekayo, 2004), ukudlala imidlalo yevidiyo (I-Koepp okqhubekayo, 1998; Hoeft okqhubekayo, 2008kunye nokubonakala kokuthanda ukutya (wang okqhubekayo, 2004a) isebenze uninzi lweengingqi ezifanayo zobuchopho (okt, inkqubo ye-mesocorticolimbic kunye ne-amygdala eyandisiweyo) njengeziyobisi zokuxhatshazwa (Volkow okqhubekayo, 2004). Eli nqaku liza kuphonononga ubungqina bokuqala bokuba abaqinisi bendalo bayakwazi ukukhokelela ekuziphatheni kunye nokusebenza kwengqondo okuhlala kukhumbuza uhlengahlengiso olubonwe emva kokubhengeza iziyobisi zokuxhatshazwa, ngakumbi ii-psychostimulants. Ukulungiselela uphononongo lwangoku, ubukho beplastiki buya kuchazwa ngokubanzi njengalo naluphi na uhlengahlengiso kwindlela yokuziphatha okanye umsebenzi we-neural, similar kusetyenziso lwegama elichazwe ekuqaleni nguWilliam James (I-James, 1890). I-Synaptic plastikiity iya kubhekisa kutshintsho kwinqanaba le-synapse, ngokomlinganiselo ukulinganisa kusetyenziswa iindlela zombane (umzekelo, utshintsho kwi-AMPA / NMDA ratio). Ubume beplanethi ye-Neurochemical iya kubhekisa kwi-neurotransuction eguqulweyo (i-synaptic okanye intracellular) yokulinganisa i-biochemically ngumahluko kumanqanaba asisiseko okanye akhutshiweyo we-transmitter, receptor, okanye transporter, okanye ngokutshintsha okuguqukayo kwimeko ye-phosphorylation yayo nayiphi na kwezi molekyuli. Ubukho beplastiki yokuziphatha buya kubhekisa kulo naluphi na utshintsho kwindlela yokuziphatha (imizekelo eliqela kuxutyushwa ngayo kwiCandelo 1.1).

Imijikelezo esekwe ngaphakathi efaka imbuyekezo yendalo yemivuzo kucingelwa ukuba "ixhwilwe" ngamachiza okuphatha gadalala, kwaye iiplasitiki kwezi zisekethe kukholeleka ukuba zinoxanduva lokuziphatha okuhle (okt kufuna iziyobisi nokulangazelela) isimilo sobukrelekrele (IKelley kunye neBerridge, 2002; Aston-Jones noHarris, i-2004; IKalivas kunye ne-O'Brien, 2008; Wanat okqhubekayo, 2009b). Ubungqina kolu hlaselo lubonwa ngeendlela ezininzi zeplasitiki kwimimandla yobuchopho eyaziwayo echaphazela inkuthazo, umsebenzi wesigqeba, kunye nokulungisa umvuzo (IKalivas kunye ne-O'Brien, 2008; UTomas okqhubekayo, 2008; Frascella okqhubekayo, 2010; Koob noVolkow, i-2010; UPierce noVanderschuren, 2010; IsiRashiya okqhubekayo, 2010). Iimodeli zezilwanyana zisinike umfanekiso-ngqondweni wotshintsho olunzulu olunokuthi luhambise ngokuphathwa kwamachiza okuphathwa gadalala. Uhlengahlengiso ukusuka kuluhlu oluguqulweyo lwe-neurotransmitter ukuya kwi-cell morphology eguqulweyo kunye notshintsho kumsebenzi wokukhuphela (URobinson noKolb, i-2004; Kalivas okqhubekayo, 2009; IsiRashiya okqhubekayo., 2010). Amaqela aliqela achaze iziyobisi zokusebenzisa gwenxa ukuguqula i-synaptic plasticity kwimimandla ephambili yobuchopho ebethelelwa kwikhoboka leziyobisi (ukuphinda ujonge, bona (I-Winder okqhubekayo, 2002; IKauer kunye neMalenka, i-2007; ILuscher kunye neBellone, 2008; UTomas okqhubekayo., 2008). Uninzi lwe-neuroadaptations echaziweyo ibikwimimandla yenkqubo ye-mesocorticolimbic kunye ne-amygdala eyandisiweyo (IGrueter okqhubekayo, 2006; ISchramm-Sapyta okqhubekayo, 2006; IKauer kunye neMalenka, i-2007; Kalivas okqhubekayo., 2009; Koob noVolkow, i-2010; IsiRashiya okqhubekayo., 2010; Mameli okqhubekayo, 2011).

Ngokusekwe kwindima eyaziwayo yale mimandla kummiselo wemozulu, ukuqhubekeka kwembuyekezo yemvelo, kunye nokuziphatha okukhuthazwayo, kukholelwa ngokubanzi ukuba obu buchwephesha busisiseko seenguqu ezingalunganga kwindlela yokuziphatha ehambelana nokulutha. Ebantwini, ezinye zezo nguqu zibandakanya ukwenza izigqibo ezingalunganga, ukunciphisa ulonwabo kwimivuzo yendalo (anhedonia), kunye nokunqwenela (Majewska, 1996; Bechara, 2005; I-O'Brien, 2005). Kwimodeli yezilwanyana, ezi ndlela zitshintshiweyo zinokufundwa ngamanyathelo okuziphatha ngokulandela imbali yolawulo lwamachiza, kwaye iingingqi zobuchopho ezinengqondo zithathwa njengezokulamla la manyathelo (UMarkou noKoob, 1991; UShamham okqhubekayo, 2003; I-Bevins kunye ne-Besheer, 2005; IWinstanley, 2007). La manyathelo abonelela isiseko sovavanyo lokuthathwa kwonyango lwasokhemesti olunokuba luncedo kunyango lokulutha.

Ubungqina bamva nje bucebisa ukuba iziyobisi ezingengabo iziyobisi zinokukhokelela kwi-neuroadaptations efanayo naleyo ichazwe ngokusetyenziswa gwenxa kweziyobisi. Ngelixa uninzi lwale mizekelo yeplastiki ivela kwizifundo zezilwanyana, iingxelo zibandakanya nemizekelo kwizifundo zabantu.

Kolu phononongo, siza kuphanda umba wokuba imbuyekezo yendalo iyakwazi ukwenza into ye-neural kunye nokuziphatha ngendlela ye-analog kwi-drug drug. Uphononongo lwexesha elizayo malunga nale nto inokusinika ukuqonda malunga nokuziphatha kunye nokukhuthaza amayeza "ezonyango" anokuthi axhamle kweziyobisi nakwezona ziyobisiFrascella okqhubekayo., 2010).

1.1. Iithiyori zokuziphatha kunye nokulutha kweziyobisi

Kwicandelo lokusetyenziswa kweziyobisi, iithiyori ezahlukeneyo ziye zavela zichaza indlela ubukho beplastikhi kunye neendlela zokuziphatha zinegalelo ekwenzeni iziyobisi. Enye ithiyori kukukhuthaza ubuntu (URobinson noBerridge, i-1993, 2001, 2008). AUkulandela le thethi, kubantu abachaphazeleka lula, ukubhengeza iziyobisi okuphindaphindiweyo kukhokelela ekuvuseleleni (ukunyamezelana umva) kwezikhuthazo zepropathi yokukhuthaza iziyobisi kunye nezinto ezinxulumene neziyobisi. Olutshintsho okungenani kubunxalenye belamli lwe-nucleus accumbens (NAc) dopamine (DA) yokukhutshwa emva kokubhengeza iindlela ezinxulumene neziyobisi.. Ngokuziphatha, oku kunxulunyaniswa nokwanda kokufuna kunye nokunqwenela iziyobisi xa umntu evezwa kwimikhwa enxulumene nokutya (okt umbhobho wokuqhekeka). Kwimodeli yezilwanyana, imvakalelo yokhuthazo inokumodareyithwa ngokulinganisa indlela yokuziphatha kweziyobisi ekuphenduleni kwimikhwa ehambisana nolawulo lweziyobisi (URobinson noBerridge, i-2008). Imvakalelo ye-locomotor nayo yenzeka ngolawulo oluphindaphindiweyo lweziyobisi ezininzi zokuxhatshazwa kwaye inokuba ngumgaqo ongathanga ngqo wovuselelo lwenkuthazo, nangona ukuthambekisa kunye novuselelo lwenkuthazo ziinkqubo ezingahambelaniyo (URobinson noBerridge, i-2008). Ngokukodwa iinkqubo zokuphucula ubuntununtunu zinokuguqulela phakathi kwamabhaso neziyobisi ezingezozamachiza (UFiorino noPhillips, 1999; IAvena kunye neHoebel, 2003b; URobinson noBerridge, i-2008). Emntwini, indima yokubonakalisa i-dopamine ukubonakalisa iinkqubo zokuvuselela amandla okuvuselela ubukho butsha nje kukuqaqanjelwa kokujongwa kwesifo sokudakumba (dopamine dysregulation syndrome) kwezinye izigulana ezithatha amachiza e-dopaminergic. Esi sifo siphawuleka ngokunyuka okunyanzeliswa ngamayeza (okanye ngokunyanzelwa) kwimivuzo engeyiyo yeziyobisi njengokungcakaza, ukuya ezivenkileni, okanye ezesondo (Evans okqhubekayo, 2006; I-Aiken, i-2007; ILader, 2008).

Enye ithiyori ephuhlisiweyo ukuchaza indlela ukuhambelana kwesiyobisi kunceda ekubeni likhoboka yinkqubo yeqela elichasayo (USolomon, 1980; Koob okqhubekayo, 1989; UKoob noLe Moal, i-2008). Ngokufutshane, le ngcingane yenkuthazo ithi kukho iinkqubo ezimbini ekubhekiswa kuzo ngamava aphindaphindiweyo: eyokuqala ibandakanya ukubandakanyeka ekuhlaleni okanye inkqubo ye-hedonic, inkqubo yesibini kukurhoxa (USolomon kunye noCorbit, 1974). Umzekelo onikezwe nguSolomon onxulumene nokusetyenziswa kwe-opiate, apho ukunyamezelana kuphuculwe khona kwiziphumo ze-hedonic emva kokuvezwa okuphindaphindiweyo kweziyobisi, kunye neempawu ezimbi zokurhoxa kuya kuvela okuya kukhuthaza ngakumbi ukusetyenziswa kweziyobisi (ukuqiniswa okungalunganga) (USolomon, 1980). Olu hlobo lwakwangoko lwethiyori lwasungulwa ngenjongo yokuchaza indlela yokuziphatha eguqulweyo ngokufumana zombini iziyobisi kunye nembuyekezo engeyiyo yeziyobisi (ukuphinda ujonge, bona (USolomon, 1980)). Ukonyuka ithiyori yenkqubo yeqela elichasayo yimodeli ye-allostatic yeenkqubo zengqondo ezishukumisayo (UKoob noLe Moal, i-2001, 2008). BNgokufutshane, le modeli ibandakanya iingcinga ezichaseneyo zomvuzo kunye nokuchasana nomvuzo, ngelixa le yokugqibela ibandakanya ukusilela ukubuyela kwikhaya elibekiweyo, elikhokelela kwimpembelelo embi nasekunciphiseni umvuzo wendalo, okonyusa ukhuthazo lokukhulula eli lizwe (UKoob noLe Moal, i-2008). Ubungqina be-neuroplasticity elilawula eli lizwe litshintshileyo linokubakho livela kwiziphumo ezininzi, kubandakanywa dI-basal NAc DA kulandela ukurhoxiswa kweziyobisi kwiigundane (Weiss okqhubekayo, 1992), ukwehla kwe-striatal D2 receptors kwi-striatum kunye ne-accumbens yeziyobisi ezinxilisayo zabantu kunye neziyobisi ze-heroin ezithintekayo (Volkow okqhubekayo., 2004; Zijlstra okqhubekayo, 2008), kunye nokunyuka okubumbayo kwe-intracranial self-stimulation (ICSS) ngexesha lokurhoxiswa kwe-cocaine kumagundane (UMarkou noKoob, 1991). Ukongeza kwiinguqulelo kwi-mesolimbic DA signing, iinkqubo zoxinzelelo oluphambili ziyaqeshwa. Umzekelo wokomelela ngakumbi kukwandiswa kweCRF kwi-hypothalamus, kumbindi we-amygdala, kunye nebhedi yendawo yesitalia emva kokurhoxiswa kwamachiza amaninzi okuphathwa gadalala. (UKoob noLe Moal, i-2008).

Ithiyori yesithathu yokuchaza i-neuroplasticity enegalelo kumlutha kukuqeshwa kwe-neurocircuitry esekwe kwimikhwa yokuboniswa iziyobisi okuphindaphindiweyo (Everitt okqhubekayo, 2001; Everitt okqhubekayo, 2008; IGreybiel, i2008; I-Ostlund kunye neBalleine, 2008; UPierce noVanderschuren, 2010). Umzekelo, umntu ongengomntu ulungiselela ukutshintsha kwe-cocaine ye-glucose kunye namanqanaba e-dopamine D2 receptor kunye ne-dopamine transporter ethe ichaphazela i-stralatum ye-ventral, kodwa ngokunyusa ukubonakaliswa okwandayo kwi-dorsal striatum (Iporrino okqhubekayo, 2004a; Iporrino okqhubekayo, 2004b). Olu lwandiso "lubonisa ukuba izinto ezenziwa kukuziphatha ngaphandle kwempembelelo yecocaine zincinci kwaye zincinci ngokunyuka kwexesha lokuchaphazeleka ekusebenziseni iziyobisi okukhokelela kulawulo lwecocaine kuzo zonke iinkalo zobomi bomlutha" (Iporrino okqhubekayo., 2004a). Oku kuqhubekela phambili kweplasitiki ukusuka kwangaphakathi ukuya kwimbonakalo yendlela yokusebenza kuyahambelana noncwadi oludala kwinguqulelo ukusuka kwinjongo- ukuya kufundo olusekwe kumakhaya (I-Balleine kunye ne-Dickinson, i-1998) kwaye ine-anatomical ehambelana nayo exhasa ubuchule bemfundo esekwe kumvuzo ukuze ibandakanye inkqubela phambili ngakumbi kumanqaku omtshato (iindaba okqhubekayo, 2000).

2. Umvuzo wokutya

Mhlawumbi owona msebenzi ufundwe kakhulu kukutya. Ukutya kungumvuzo ophindwe kabini kwizifundo ezininzi ezinokusetyenziswa kwaye zisetyenziselwe ukomelela kwiinkqubo ezifana nokusebenza (ukuzilawula) kwimisebenzi, iimvavanyo zombaleki, ukufundwa kwe-maze, imisebenzi yokungcakaza, kunye nemeko yendawo (Isikhumba, i-1930; I-Ettenberg kunye neCamp, 1986; Kandel okqhubekayo, 2000; Kelley, 2004; Tzschentke, 2007; UZebhe okqhubekayo, 2009). Kwiigundane eziqeqeshelwe ukucinezela i-lever ukuba ifumane ukuzilawula ngokwamachiza, ukutya okunokuthenjwa okuneswekile kunye nesalcharin kuboniswe ukunciphisa ukuzilawula kwe-cocaine kunye ne-heroin (UCarroll okqhubekayo, 1989; I-Lenoir kunye ne-Ahmed, i-2008), Kunye ezi zokuqiniswa kwendalo zibonakalisiwe ukuba zikhuphe i-cocaine ekukhetheni ukuzilawula kwisininzi samagundane kuvavanywa (Lenoir okqhubekayo, 2007; Cantin okqhubekayo, 2010). Oku kungacebisa ukuba ukutya okumnandi kunexabiso eliphezulu lokuqinisa kune-cocaine, nakwizilwanyana ezinembali ebanzi yokutya iziyobisi. (Cantin okqhubekayo., 2010). Ngelixa le meko inokuthi ivele njengobuthathaka kwiimodeli zangoku ze-cocaine, iincinci ezincinci zikhetha i-cocaine iswekile okanye i-saccharin (Cantin okqhubekayo., 2010). Kungenzeka ukuba ezi zilwanyana zinokumela inani labantu “abasesichengeni”, elichaphazela imeko yabantu. Le ngcinga iphononongwa ngakumbi kwiNgxoxo (Icandelo 6.1).

Umsebenzi ovela kwielebhu ezininzi ubonakalise imizekelo yokuplastiki kwimijikelezo enxulumene nomvuzo emva kokufumana ukutya okufumanekayo. Ukuziqhelanisa nezinto ezinokulandelwa emva kwembali yokutya ukutya okuthe chatha kuye kwafaniswa nezo zijongwe emva kweziyobisi zokuphathwa gadalala, zenza izazinzulu ezininzi zacebisa ukuba ukusela ukutya kungafani nokulutha. (Hoebel okqhubekayo, 1989; I-Magnen, i-1990; wang okqhubekayo., 2004b; IVolkow kunye neWise, 2005; UDavis noCarter, 2009; UNair okqhubekayo, 2009a; I-Corsica kunye nePelchat, 2010). Ilabhoratri kaBartley Hoebel inedatha ebanzi ebonisa ubuntu beplastikhi emva kwembali yokufikelela kwiswekile, nto leyo ikhokelele yena kunye nabalingane bakhe ukuba bacebise ukuba iswekile ehlangabezana nenqobo yokulutha (Oats okqhubekayo, 2008). Olu luvo luxhaswa yi Inyaniso yokuba imizekelo eliqela yokubonakaliswa emva kwesiyobisi ephindaphindiweyo ichazwa njengendawo yokufikelela hayi kuphela iswekile, kodwa namafutha. Iindidi ezahlukeneyo zokutya okunencasa zisetyenziselwe ukufunda iplasitiki, kubandakanywa iswekile eninzi, amanqatha aphezulu, kunye “neNtshona” okanye i- “Cafeteria” ukutya ukuzama ukumisela iindlela ezahlukeneyo zokutya.

Olunye uphawu lweplastikini ebangelwa kukutya kukuba "uvavanyo-mfanekisoUmsebenzi wentloko yothutho phakathi kokutya iswekile kunye nezifo zengqondo zinokuphembelela nangayiphi na indlela yonyango. (IAvena kunye neHoebel, 2003b, a; IGosnell, 2005). Ukubonakalisa imvakalelo yomnqamlezo yinto eyenzeka emva kokuvezwa kwendawo engqongileyo okanye yezechiza (ezinje ngoxinzelelo okanye isifo sokusebenza kwengqondo, ngokulandelelana) esikhokelela kuphuculo oluphuculweyo (oluqhelekileyo locomotor) kwiarhente eyahlukileyo yokusingqongileyo okanye yezechiza.Umfo okqhubekayo, 1980; O'Donnell kunye noMiczek, ngo-1980; Kalivas okqhubekayo, 1986; UVezina okqhubekayo, 1989). Iinkqubo zesensitization ezibandakanya ii-psychostimulants zibandakanya i-mesolimbic DA neurons, kunye ne-sensitization yendlela yokunqamleza kukholelwa ukuba ivela kwiinkqubo eziqhelekileyo zesenzo phakathi kokukhuthaza ezimbini (Umfo okqhubekayo., 1980; Herman okqhubekayo, 1984; UKalivas noStewart, i-1991; I-self kunye ne-Nestler, 1995).

Ukuvuselela iminqamlezo kwii-psychostimulants kukwabonwa nakwizilwanyana ezondliwe ngokutya okuneswekile eninzi / ukutya okunamafutha ngexesha lokuxinana nasemva kokulunyulwas (Shalev okqhubekayo, 2010). Ukufumanisa ukuba ukubonakaliswa kokutya okunamafutha aphezulu kunokuguqula "ukuvuza" (ukuqinisa) imiphumo yesiyobisi sokuxhatshazwa, uDavis et al. izilwanyana ezivavanyiweyo zondla ukutya okunamafutha aphakamileyo ukuze kuguqulwe imvakalelo yokuziva uthibile usebenzisa imeko ekhethiweyo yendawo (CPP) paradigm (Davis okqhubekayo, 2008). Kule modeli, izilwanyana ziyavunyelwa kuqala ukuba zihlole izixhobo zegumbi elininzi (uvavanyo lwangaphambili) apho igumbi ngalinye linemiboniso ebonakalayo, ethambileyo, kunye / okanye i-olonicory cues. Ngexesha leseshoni zokuhlela, izilwanyana zivalelwa kwelinye lamagumbi kwaye zihanjiswe ngomvuzo (umzekelo, inaliti ye-amphetamine okanye ukutya kwigumbi). Ezi seshini ziphindaphindwa kwaye zidityaniswa kunye neeseshoni zokujonga imeko ezibandakanya ukubhanqa kwelinye igumbi lezixhobo ngemeko yolawulo (umz. Inaline yenaliti okanye akukho kutya). Isigaba sovavanyo senziwa phantsi kweemeko ezifanayo nezovavanyo langaphambi kovavanyo kunye ne-CPP ibonakaliswa xa izilwanyana zibonisa ukhetho olukhethekileyo kwigumbi elinombhalo wesiyobisi okanye umvuzo ongenguwo iziyobisi. UDavis et al. ifumanise ukuba iigundane ezinamafutha amaninzi zityebile ukungaphuhlisi imeko ekhethiweyo ye-amphetamine, iphakamisa ukunganyamezeli phakathi kokutya okuphezulu kwamafutha kunye nemeko yokuqinisa imeko yeamphetamine (Davis okqhubekayo., 2008).

Ukongeza ekuziphatheni kweplastiki yokuziphatha, ukuthoba kakhulu iintlobo ezithile zokutya kuye kwanxulunyaniswa nokuqina kweplastic ye-neurochemical. Ngokukodwa, i-dopamine kunye ne-opioid signaling ibonakala ngathi inokuchaphazeleka kulungelelwaniso emva kokungena ukufikelela kwishukela eliphezulu okanye ukutya okunamafutha aphezulu. Kwi-NAc, iziqendu ezondlayo ezinokubakho kwiswekile kunye nokonyusa i-D1 kunye nomxholo we-receptor we-D3. (nokuba ngu-mRNA okanye iproteni), ngelixa kuncitshiswa ii-receptors ze-D2 kwi-NAc kunye ne-drial striatum (Colantuoni okqhubekayo., 2001; Bello okqhubekayo, 2002; Ispange okqhubekayo, 2004). Esi siphumo saye saqwalaselwa ngokufikelela okwandileyo kokutya okunamafutha aphezulu kwiigundane, kunye Ukwehla okukhulu kwe-D2 kwenzeka kweyona rakhi inzima kakhulu (UJohnson noKenny, i-2010). Ezi Uhlengahlengiso kwii-recopal dopamine ezityhutyhayo kunye ne-striatal dopamine zihambelana nezo zibonwa kwiintonga ezenziwa rhoqo ngecocaine okanye morphine (Iialboti okqhubekayo, 1993; I-Unterwald okqhubekayo, 1994a; Ispange okqhubekayo, 2003; Conrad okqhubekayo, 2010). Ukongeza, ukuncitshiswa kwama-receptor e-striatal D2 kukwabonwa nakubasebenzisi abasebenzisi be-psychostimulant kunye nezotywala (Volkow okqhubekayo, 1990; Volkow okqhubekayo, 1993; Volkow okqhubekayo, 1996; Zijlstra okqhubekayo., 2008), nakubantu abadala abadala, apho umxholo we-D2 wafunyanwa ukungalungelelanisi kakuhle kunye nesalathiso sobunzima bomzimba (wang okqhubekayo., 2004b). Ukubonakaliswa kwe-opioid signaling kuchaphazeleka kakhulu kukutya (UGosnell noLeviine, 2009). Iswekile engaphakathi okanye ukutya okumnandi / okunamafutha kunyusa i-opioid receptor yokubopha kwi-NAc, cingate cortex, hippocampus kunye ne-locus coeruleus (Colantuoni okqhubekayo., 2001) kunye nokucutha i-enkephalin mRNA kwi-NAc (Kelley okqhubekayo, 2003; Ispange okqhubekayo., 2004). Ubukho beplastiki ye-Neurochemical kwi-mesolimbic DA kunye ne-opioid signaling nayo ibonakalisiwe ukuba yenzeke kwinzala yeempuku zowesetyhini ezondliwe ngamafutha aphezulu ngexesha lokukhulelwa (IVucetic okqhubekayo, 2010). Ezi nzalo ziphakamise i-dopamine transporter (i-DAT) kwindawo ye-ventral tegmental (VTA), i-NAc, kunye ne-preortal cortex (PFC), kunye nokunyuka kwe-preproenkephalin kunye ne-mu opioid receptors kwi-NAc kunye ne-PFC (IVucetic okqhubekayo., 2010). Into enomdla kukuba, olu tshintsho lwalunxulunyaniswa notshintsho lwe-epigenetic (hypomethylation) yezinto zokukhuthaza kuzo zonke iiproteni ezichaphazelekayo.

Iziphumo kwinkqubo ye-corticotropin-releasing factor (CRF) ngamafutha aphezulu / ukutya okuneswekile eninzi zikwakhumbuza nezo zingeniswe ziyobisi zokuxhatshazwa. I-CRF kwi-amygdala yanda ngokulandela ukurhoxiswa kweyure ye-24 kwisidlo esinamafutha aphezulu, ngelixa izilwanyana ezigcinwe kule ndlela yokutya zazingafakwanga amygdala CRF (Teegarden neBale, i-2007). Kwimodeli yangaphambi kokubonwa, oku kuguqulwa kweCRF etshintshayo kucingelwa ukuba kuqhutywa iinkqubo zokuqiniswa ezingezizo kunye nokwanda kokungena "kokuzonwabisa" kwe-ethanol (I-Koob, i-2010). Ngenxa yoko, abachasi beCRF bacetywayo malunga nokunyangwa butywala neziyobisi.Sarnyai okqhubekayo, 2001; Koob okqhubekayo, 2009; Ezantsi kunye noTiele, 2010). Ngokusekwe kule datha, abachasi beCRF banokulindeleka ukuba bancede abantu ukuba bangahlali kumanqatha aphezulu / kukutya okuneswekile eninzi ngexesha lokutshintsha kokutya okusempilweni.

Izinto ezikhutshelweyo lolunye udidi lweemolekyuli ezigxininisa ekuphembeleleni kwiziphumo zokunyangwa kwamachiza okuphathwa gadalala ngokuchaphazela ngqo ukubonakaliswa kwesini (McClung noNestler, 2008). Ukuxhasa umbono wokuba ukutya kuyakwazi ukubambelela kwi-neural plasticity, izinto ezininzi ezikhutshelweyo nazo ziyaguqulwa ngokutya. I-NAc phospho-CREB yancitshiswa iiyure ezingama-24 kulandela ukurhoxa kwisidlo esikhulu se-carbohydrate kwaye zombini iiyure ze-24 kunye neveki ye-1 emva kokurhoxiswa kokutya okunamafutha aphezulu, ngelixa into ekhutshelweyo ye-delos FosB iyanda ngexesha lokufikelela kokutya okunamafutha aphezulu (Teegarden neBale, i-2007) okanye sucrose (Wallace okqhubekayo, 2008). Kwi-NAc, i-phospho-CREB ehlileyo iyabonakala ngexesha lokurhoxa kwi-amphetamine kunye ne-morphine (McDaid okqhubekayo, 2006a; McDaid okqhubekayo, 2006b), I-delta FosB nayo iyakhula ngokulandela ukurhoxiswa kula machiza kunye necocaine, i-nicotine, i-ethanol, kunye ne-phencyclidine (McClung okqhubekayo, 2004; McDaid okqhubekayo., 2006a; McDaid okqhubekayo., 2006b). Ngokufana nendima yabo ecetywayo ekwandiseni indlela yokuziphatha kweziyobisi, ezi neuroadaptations zinokuchaphazela nendlela ekusetyenzwa ngayo kokondla, njengoko ukugcwala kwe-FosB kwimoqo yonyuselo-moya yonyusa ukukhuthaza ukufumana ukutya (Olausson okqhubekayo, 2006) kunye ne-sucrose (Wallace okqhubekayo., 2008).

I-Synaptic plastikiity kwi-circry enxulumene nomlutha inxulunyaniswe nayo kwi vivo Ukulawulwa kwamachiza amaninzi okuphathwa gadalala. Kwi-VTA, iiklasi ezininzi zeziyobisi, kodwa hayi iziyobisi zengqondo ezingasebenziyo zibangela ukuba kube ngathi kuhambelana ne-synaptic plasticity (Isalali okqhubekayo, 2003; Stuber okqhubekayo, 2008a; Wanat okqhubekayo, 2009a). Ukuza kuthi ga ngoku, kukho idatha encinci kakhulu yokulinganisa ngokuthe ngqo iimpembelelo zokutya kwi-plastiki ye-synaptic kwi-neurocircuitry enxulumene nomlutha. Isifundo sokusebenza esisebenzayo esidityaniswa nokutya (i-chow okanye i-sucrose pellets) sonyusa umyinge we-AMPA / NMDA kwindawo ye-ventral yohambo ukuya kuthi ga kwiintsuku ezisixhenxe emva koqeqesho (Chen okqhubekayo, 2008a). Xa i-cocaine yayinakho ukuzilawula, isiphumo sayo saqhubeka ukuya kwiinyanga ezintathu, kwaye le miphumela ayizange ibonwe ngokuphathwa nje kwe-cocaine (Chen okqhubekayo., 2008a). Ubuncinci bexesha le-EPSP ejikelezayo kwi-VTA nayo yonyuswe ukuya kuthi ga kwiinyanga ezintathu emva kokuzilawula kwe-cocaine, ukuya kuthi ga kwiiveki ezintathu emva kokuzilawula (kodwa hayi chow) ukuzilawula, icebisa ukuba ukusayinwa kwe-glutamatergic kuqiniswa ngaphambi nasemva kokulandelelana.Chen okqhubekayo., 2008a).

Ezi datha zibonisa ukuba amanyathelo athile e-synaptic plasticity kwinkqubo ye-mesolimbic (umzekelo, i-AMPA / NMDA ratios) inokunxulunyaniswa nokufunda okomdla ngokubanzi. Oku kuxhaswa sisibakala sokuba ukufunda kwePavlovian kunxulunyaniswa nomvuzo wokutya okubonisiweyo kwi-VTA LTP ngexesha lokufunyanwa (ngemini ye-3 yemeko yokulungisa imeko) (Stuber okqhubekayo, 2008b). Nangona ubungqina beplastiki babonwa ngemini ye-3, babengekho ngeentsuku ezimbini kamva, becebisa ukuba ukuzilawula ngokucacileyo kukhokelela ekunyamezeleni ukububuninzi beplastiki kwezi zisekethe (Stuber okqhubekayo., 2008b). Oku kubonakala kukwimeko yokuba yiplasitiki enxulumana nokuzilawula kwe-cocaine, njengoko iphindaphindwe engenakuphikiswa yecocaine-ye-cocaine kwi-VTA nayo ihlala ixesha elifutshane (Borgland okqhubekayo, 2004; Chen okqhubekayo., 2008a). Uhlobo lwezi zifundo zokusebenza aziyi, nangona kunjalo, isaphulelo isibakala sokuba ukufikelela okuthe chatha kokutya okunokutya kunokukhokelela kukhuselo lweplastiki ye-synaptic. Ngexesha lezifundo eziqhelekileyo zokusebenza, izilwanyana ziyavunyelwa ukuba zifikelele kumvuzo wokutya kunangexesha lokufumana ukutya simahla okanye ukufikelela. Izifundo zexesha elizayo ziya kufuneka zenziwe ukujonga iziphumo zokufikelela kokutya okufumaneka ngokusemgangathweni kwi-plastiki ene-synaptic.

3. Umvuzo wesini

Ukwabelana ngesondo ngumvuzo othi, kakhulu njengokutya, kubalulekile ekusindisweni kohlobo. Njengokutya kunye neziyobisi ezininzi zokuxhatshazwa, indlela yokuziphatha ngokwesondo iphakamisa i-mesolimbic DA (Meisel okqhubekayo, 1993; Mermelstein noBrakker, 1995). Ikwayindlela yokuziphatha elinganiswe ngokokuqiniswa kwexabiso ngumsebenzi (Ibhantshi neJordan, i-1956; I-Caggiula kunye neHoebel, i-1966; Everitt okqhubekayo, 1987; Crawford okqhubekayo, 1993kunye neendlela zokujonga imeko (I-Paredes kunye neVazquez, 1999; UMartinez kunye neParedes, i-2001; Tzschentke, 2007). Izifundo zabantu kunyango lokuziphatha ngokwesondo okunyanzelekileyo (okuhlulwe njenge- "Disgency Disney Not Not Specified" kwi-DSM-IV) baneempawu ezininzi ezinxulunyaniswa nokusetyenziswa kweziyobisi, kubandakanya ukwanda, ukurhoxa, ubunzima ekuyekeni nasekunciphiseni umsebenzi, kwaye uqhubeke nokuziphatha ngokwesondo nangona kuchasene iziphumo (IOrford, 1978; Igolide kunye neHeffner, 1998; UGarcia kunye noTibaut, 2010). Ukujonga oku kulungelelwaniso kwindlela yokuziphatha, kusengqiqweni ukuba nomfanekiso ngqondweni we-neuroadaptations eyenzeka ngaphakathi kwe-mesocorticolimbic circry. Njengoko kubonwa kuboniswa rhoqo iswekile, ukudibana okuphindaphindiweyo ngokwesini kwiigundane ezingamadoda kuhanjiswe nge-amphetamine kwi-assomotor assay (Pitchers okqhubekayo, 2010a). Ukudibana okuphindaphindiweyo ngokwesondo kukonyusa ukusetyenziswa kwe-sucrose kunye nokukhetha indawo ye-amphetamine yodosi ephantsi, ukucebisa ukuthambeka komnqantsa phakathi kwamava ezesondo kunye nomvuzo wamachiza. (Wallace okqhubekayo., 2008; Pitchers okqhubekayo, 2010b). Iyafana nakwimvakalelo evuselelayo yeziyobisi zokuxhatshazwa (I-Segal kunye neMandell, i-1974; URobinson kunye no-Becker, 1982; URobinson noBerridge, i-2008), ukudibana okuphindaphindiweyo ngokwesini kuvuselela impendulo ye-NAc ye-DA kwisini esithe saphinda sahlangana (I-Kohlert kunye neMeisel, 1999). Imvakalelo yokuwela umnqamlezo ikwanika ingxelo ngokwembali, njengoko imbali yolawulo lwe-amphetamine iqhuba indlela yokuziphatha ngokwesondo kunye nokunyusa ukwanda okuhambelana nayo kwi-NAc DA (UFiorino noPhillips, 1999).

AUkuchazwa komvuzo wokutya, amava ezesondo nawo kunokukhokelela ekusebenziseni iicascades ezinxulumene neplastity. Into ekhutshelweyo yeFosB iyakhula kwi-NAc, kwi-PFC, kwi-drial striatum, nakwi-VTA emva kokuziphatha okuphindaphindiweyo ngokwesini. (Wallace okqhubekayo., 2008; Pitchers okqhubekayo., 2010b). Olu nyuso lwendalo kwi-delta FosB okanye ubuchwephesha bentsholongwane egxile kwi-delta FosB ngaphakathi kwe-NAc modulates ukusebenza kwezesondo, kunye ne-NAc blockade ye-delta FosB ifumanisa le ndlela yokuziphatha (Hedges okqhubekayo, 2009; Pitchers okqhubekayo., 2010b). Ngapha koko, ukugcwala kwentsholongwane yeflash FosB kuphucula imeko ekhethwayo yendawo ebhangqwe ngamava ezesondo (Hedges okqhubekayo., 2009).

The I-MAP kinase isibonisa umendo yenye indlela enxulumana neplastiki eyabanjwa ngexesha lamaxesha abelana ngesondo (Bradley okqhubekayo, 2005). Mnan Abasetyhini abanamava ngokwabelana ngesondo, ukudibana ngesondo kukhokelele ekunyuseni kwe-PERK2 kwi-NAc (I-Meisel ne-Mullins, i-2006). Ukonyuka kwe-NAc pERK kubangelwa ziyobisi ezininzi zokuxhatshazwa, kodwa kungezizo iziyobisi ezingekhoyo kweziyobisi, okucebisa ukuba ukwenziwa kwe-NAc ERK kunokuba nokudibana neplastiki ehambelana nokulutha. (Isiphawuli okqhubekayo, 2004). Ukongeza, uphononongo lwakutsha nje lufumanise ukuba i-pERK yavuselelwa zizenzo zesondo kwimizwa efanayo ye-NAc, i-basolateral amygdala, kunye ne-anterior cingulate cortex ebekade yenziwe i-methamphetamine (Frohmader okqhubekayo, 2010). Olu khetho lodwa lubonisa ukuba ukwenza lo msebenzi wokubonisa ikhasethi kwi-NAc nakweminye imimandla ye-mesocorticolimbic kungakhokelela ngokuthe ngqo kubukho beplastiki ekhuthaza ukungabi namdla kokuziphatha kwexesha elizayo (Igirafu okqhubekayo, 2007).

Ubume be-Neural kwinkqubo ye-mesocorticolimbic nayo iyatshintshwa emva kwamava ezesondo. I-Pitchers kunye nabalingane kutshanje baye baxela ukwanda kwe-dendrites kunye ne-dendritic spines kwi-NAc kumagundane ngexesha lokurhoxisa (Pitchers okqhubekayo., 2010a). Tukwandisa enye idatha ebonisa ukuba amava ezesondo anokutshintsha i-morendology dendritic ngendlela enomdla ekuvezeni iziyobisi okuphindaphindiweyo (UFiorino noKolb, 2003; URobinson noKolb, i-2004; I-Meisel ne-Mullins, i-2006).

4. Umvuzo womzimba

Ukufikelela kwisondo eliqhuqhelwayo lokuzivocavoca kusebenza njengokuqiniswa kweentonga zelebhu (Belke kunye noHeeman, 1994; Belke kunye Dunlop, 1998; Ileta okqhubekayo, 2000). Njengamachiza okuphatha gadalala kunye neminye imivuzo yendalo, ukuzivocavoca kwiintonga kunxulunyaniswa nokwanda kwe-DA kwi-NAc nakwi-striatum (Ukhululekile kunye no-Yamamoto, i-1985; Hattori okqhubekayo, 1994). Ukuzivocavoca kwakhona kuphakamisa amanqanaba obuchopho kunye ne-plasma yee-opioids eziphakathi kwabantu kunye neentonga (UChristie noChesher, 1982; UJanal okqhubekayo, 1984; I-Schwarz kunye ne-Kindermann, i-1992; UAsahina okqhubekayo, 2003). Eyona nto kugxilwe kuyo kwezi opioids yi-op opateate receptor, isiza esisiseko seziyobisi ze-opiate zokuxhatshazwa ezifana ne-heroin kunye ne morphine. Oku kugqagqana kukwabonakala ukwanda kwimpendulo yokuziphatha kweziyobisi zokuxhatshazwa. Ngokungafani nemivuzo yendalo ekuxoxwe ngayo ukuza kuthi ga ngoku, uninzi lwezifundo lufumanise ukuba ukuveza imithambo kukufumana iziphumo zeziyobisi zokuxhatshazwa. Umzekelo, ukuzilawula kwe-morphine, i-ethanol, kunye necocaine konke kuncitshiswa kokulandela umzimba (Qhobosha okqhubekayo, 2002; Smith okqhubekayo, 2008; Ehringer okqhubekayo, 2009; Hosseini okqhubekayo, 2009). Amava omzimba athabatha i-CPP kwi-MDMA kunye necocaine kunye nokunciphisa ukunyuka kwe-MDMA kwi-NAc DA (Chen okqhubekayo, 2008b; Thanos okqhubekayo, 2010). Ukuzilolonga ngaphambi koqeqesho lokulawula ukuzilawula nako kukwazile ukunciphisa ukufunwa kweziyobisi nokubuyiselwa, nangona kolu phando ukuzilawula ngokwakho kwe-cocaine kungachaphazelekanga.Zlebnik okqhubekayo, 2010). Kwisifundo esifanayo, ukukhangela i-cocaine kunye nokubuyiswa kwe-cue kuncitshisiwe kumagundane ezazilolonga ngexesha lokuyeka iziyobisi (Lynch okqhubekayo, 2010). Mnan izilwanyana ezinembali yokuqhuba ngamavili abalekayo, ukurhoxa ekufikelelekeni kwamavili kukhokelela kwiimpawu zokurhoxisa iziyobisi kubandakanya, ukunyusa uxinzelelo kunye nobukrwada, kunye nokuba semngciphekweni kwi-naloxone-yarhoxiswa kwangaphambilil (Hoffmann okqhubekayo, 1987; IKharek okqhubekayo, 2009).

Ukongeza kwiimpendulo eziguqulweyo zokuziphatha kumachiza okuphatha gadalala, kukho ukubakho kweplastic ye-neurochemical kuboniswe ngokunyuka kwe-dynorphin kwi-striatum kunye ne-NAc emva kokugijima, into ekwabonayo nakwabo baxakayo yi-cocaine nakwizilwanyana ezilandela ukulawulwa kwecocaine okanye i-ethanol. (I-Lindholm okqhubekayo, 2000; Werme okqhubekayo, 2000; Wee kunye noKoob, i-2010). Kukhumbula kwakhona iziyobisi ezinxulumene neural neplastikhi, umba wokukhutshelwa kokutya delta FosB ifakwa kwi-NAc yezilwanyana ezinamava okuqhuba ngamavili (Werme okqhubekayo, 2002). Olu tshintsho lunokwenza imeko "yokurhoxa" eqapheleke emva kokususwa kokuqhutywa kwevili kwizilwanyana ngokufikelela ngaphambili (Hoffmann okqhubekayo., 1987; IKharek okqhubekayo., 2009). Kwelinye icala, ukuzivocavoca umzimba ngexesha lokuyeka iziyobisi kukwanxulunyaniswa nokwehliswa kokuvuselelwa okuvuselelweyo kwe-ERK kwi-PFC (Lynch okqhubekayo., 2010). Esi sisiphumo esifanelekileyo ikakhulu esijongene nendima ye-ERK kwimibandela emininzi yokongezan (Isiphawuli okqhubekayo., 2004; Lu okqhubekayo, 2006; Igirafu okqhubekayo., 2007) kunye nokufumanisa ukuba ukwenziwa kwe-ERK ngaphakathi kwi-PFC kuyayanyaniswa nokwenziwa kukunqwenela iziyobisi (Koya okqhubekayo, 2009). Amanqanaba e-striatal e-dopamine D2 receptor aye axelwa nokwandisa umthambo (I-MacRae okqhubekayo, 1987; I-Foley kunye neFleshner, 2008), isiphumo esichaseneyo noku kulawula ukuzilawula ngokwasemphefumlweni kwiintonga, amalungu, kunye nabantu (Volkow okqhubekayo., 1990; Nader okqhubekayo, 2002; Conrad okqhubekayo., 2010). Kuyenzeka ukuba olu hlengahlengiso lube negalelo kwisiphumo “sokukhusela” sokuziqhelanisa malunga nokusebenzisa iziyobisi / iziyobisi. Inkxaso yale mbono ivela kwizifundo ezichazwe ngaphambili kweli candelo ibonisa ukunciphisa ukuzilawula kwamachiza, ukufuna, nokuphindisela kwizilwanyana ezivunyelwe ukuzilolonga. Kukwakhona nenkxaso yokuba ukuzivocavoca kunokukwenza “ngaphandle kokukhuphisana” ukuzilawula ngokwamachiza, njengoko ukuqhuba ivili kunciphisa umthamo we-amphetamine xa bobabini abo baqinisayo babefumaneka ngokufanayo (IKharek okqhubekayo, 1995).

Ukuzivocavoca kukwanefuthe ngaphakathi kwe hippocampus, apho kunefuthe leplastikhi (kubonakaliswa uphakamiso lwe-LTP kunye nokuphuculwa kokufunda kwesithuba) kwaye kunyusa i-neurogeneis kunye nokuchazwa kweendidi ezithile ezinxulumene neplastiki (IKharek okqhubekayo., 1995; van Praag okqhubekayo, 1999; UGomez-Pinilla okqhubekayo, 2002; Molteni okqhubekayo, 2002). Ukuncipha kwe-hippocampal neurogeneis kunxulunyaniswa nokuziphatha okufana nokudakumba kwizifundo zakwimbeleko (Duman okqhubekayo, 1999; ISahay kunye neHen, i-2007), kwaye ihambelana nokukwazi ukwandisa i-hippocampal neurogeneis, umthambo ubonakalisiwe ukuba unomphumo wokudambisa uxinzelelo kumqolo oxinzelelekileyo wamagundane (Bjornebekk okqhubekayo, 2006), kunye nokuphucula iimpawu ezixinzelelweyo kwizigulana zabantu (Ernst okqhubekayo, 2006). Ukujonga ikhonkco elidlulileyo elixeliweyo phakathi koxinzelelo lwe-hippocampal neurogeneis kunye nokwanda kwe-cocaine yokutya kunye nokuziphatha kokuziphatha kumqolo (UNonan okqhubekayo, 2010) kunye nobungqina obudlulileyo bokuba ukubonakaliswa koxinzelelo (unyango olunciphisa i-hippocampal neurogeneis), kunyusa ukubethelwa iziyobisi (ICovington neMiczek, 2005), kubalulekile ukuba ujonge iziphumo zokuzilolonga kwimisebenzi ye-hippocampal ukongeza kwezo zikumsebenzi we-mesolimbic. Kuba ukuzivocavoca kukhokelela kwiplasitiki kumjikelo wesibini onxulumene noxinzelelo (okt. Hippocampal) kunye nokujikeleza okuneziyobisi (okt inkqubo ye-mesolimbic), kunzima ukufumanisa ukuba yeyiphi na indawo “yeyeza elichasene neziyobisi” elikhoyo.

Ngokuhambelana neziphumo zokuzivocavoca kwimivuzo yamachiza, kukho ubungqina bokuba ukuqhuba kungaphungula ukuthandwa kwabaxhasi bendalo. Ngaphantsi kweemeko zokufikelela okuncinci kokutya, iigundane ezinokufikelela rhoqo kwisondo elibalekayo ziya kuyeka ukutya kude kuse ekufeni (I-Routtenberg kunye ne-Kuznesof, i-1967; IRouttenberg, 1968). Le meko igqithileyo ibonwa kuphela xa amaxesha okufikelela kokutya esenzeka ngokuqhubeka ngesondo eliqhuba, nangona oko kunokucebisa ukuba ukuvezwa kokuzilolonga kunganciphisa ukukhuthazeka ngendlela eqhelekileyo kwabo bangabisi iziyobisi kunye nabangekho iziyobisi. Ukuqwalaselwa kokugqibela kweziphumo zokuzilolonga kukuba ivili elibalekayo eligcinwe ngaphakathi kwendawo yezilwanyana linokusebenza njengendlela yokuphucula indalo. Ngelixa kunzima ukwahlula phakathi kobutyebi bendalo ukusuka ekuzilolongeni (izilwanyana ezazihlala i-EE zizivocavoca ngakumbi), iziphumo ezichaseneyo ze-EE kunye nokuzivocavoca kuxeliwe (van Praag okqhubekayo., 1999; U-Olson okqhubekayo, 2006).

5. Inoveli / Inkuthazo yokuNyusa / ukuKhulisa imeko yendalo

Inkuthazo yenoveli, ukuvuselela iimvakalelo, kunye neemeko zobutyebi eziqinisiweyo konke kuyasomeleza kwizilwanyana, kubandakanya neempuku (UVan de Weerd okqhubekayo, 1998; Besheer okqhubekayo, 1999; I-Bevins kunye neBardo, i-1999; UMellen kunye no-Sevenich MacPhee, 2001; I-Dommett okqhubekayo, 2005; UKayin okqhubekayo, 2006; I-Olsen kunye neWinder, 2009). Ubume bemeko yenoveli, ukuvusa imvakalelo, kunye nokwazisa ngendalo esingqongileyo (EE) zonke zibonisiwe ukwenza inkqubo ye-mesolimbic ye-DA (I-Chiodo okqhubekayo, 1980; Horvitz okqhubekayo, 1997; URebec okqhubekayo, 1997a; URebec okqhubekayo, 1997b; U-Wood noRebec, 2004; I-Dommett okqhubekayo., 2005; Segovia okqhubekayo, 2010), ukucebisa ukugqagqana nokujikeleza kweziyobisi. Kubuninzi babantu, imvakalelo kunye nokufuna into entsha kunxulunyaniswe nobuthathaka, ukuthabatheka, kunye nobungqwabalala bokusetyenziswa gwenxa kweziyobisi (I-Cloninger, 1987; kelly okqhubekayo, 2006); Ukujonga kwakhona, bona (I-Zuckerman, 1986). Kwimigca, ukuphendula kokunqabileyo kuye kwalungelelaniswa nolawulo olulandelayo lweziyobisi (I-piazza okqhubekayo, 1989; UKayin okqhubekayo, 2005; Meyer okqhubekayo, 2010), ephakamisa ukuba ezi zinto zimbini ze-phenotypes covary. Ngokusekwe kwezi datha kunye ne-neurochemical, kucingelwa ukuba kuninzi kakhulu kwimeksry ye-mesocorticolimbic ejikeleza impendulo kwinto engeyonyani kunye neziyobisi zokuxhatshazwa (URebec okqhubekayo., 1997a; URebec okqhubekayo., 1997b; UBardo noDwoskin, 2004). Isikhuthazo sesensory (ingakumbi ezibonakalayo kunye nezikhuthazayo) zifundiwe ukulungiselela iipropathi zazo zokuqinisa (Marx okqhubekayo, 1955; I-Stewart, 1960; UKayin okqhubekayo., 2006; Liu okqhubekayo, 2007; I-Olsen kunye neWinder, 2010), kwaye kutshanje sibonisa ukubandakanyeka kwe-dopaminergic kunye ne-glutamatergic signaling ekuchaseni iiprophathi zokuqiniswa kweshukumisi seemvakalelo ezahlukeneyo (I-Olsen kunye neWinder, 2009; Olsen okqhubekayo, 2010). Ubuninzi beplastikhi elandelayo yokuveza ukubonwa kwezinto ezinobunewunewu okanye ubungqangi boluvo ngaphakathi kwe parameter ezingayi kuphinda ziphendulelwe, nangona kukho ubungqina obukhulu bokubumbeka kwe-neural kulandela ukusebenza gwenxa okanye ukuthothiswa kwenkqubo yeemvakalelo (Kaas, 1991; I-Rauschecker, 1999; Uhlrich okqhubekayo, 2005; Smith okqhubekayo, 2009). Nangona kunjalo, kukho ubutyebi bedatha kwi-plastiki ye-neural enxulunyaniswa nezindlu kwindawo enobutyebi (ebandakanya iinkalo zezinye izihloko ekuxoxwe ngazo, kubandakanya nokungaqhelekanga kunye nokuzivocavoca;I-Kolb kunye neWhishaw, i-1998; van Praag okqhubekayo, 2000a; INithianantharajah kunye noHannan, 2006)). Ithiyori eyaziwayo ka-Hebb yokufunda ichukunyiswe ziziphumo azifumeneyo ezibonisa ukuba iigundane ezigcinwe kwindawo ephucukileyo (eyakhe indlu) ziqhuba ngcono kwimisebenzi yokufunda kunabantu abalahla inkunkuma abahlala elabhoratri (I-Hebb, 1947). Izifundo ezalandelayo zichonge utshintsho olukhulu kubunzima bobuchopho, i-angiogeneis, i-neurogeneis, i-gliogeneis, kunye nesakhiwo sokudibanisa ukuphendula kuluncedo lwendalo (EE) (UBennett okqhubekayo, 1969; Luhlaza kunye nokutshintsha, 1989; I-Kolb kunye neWhishaw, i-1998; van Praag okqhubekayo, 2000b). Idatha yakutshanje evela kwizifundo ezincinci ze-microarray zibonise ukuba izindlu ze-EE zenza ukuba kubonakale ukuba i-gene cascades ebandakanyeka yiplasitiki exhomekeke kwi-NMDA kunye ne-neuroprotection (Rampon okqhubekayo, 2000). Iqela elifanayo lafumanisa ukuba ukubonakaliswa kokusingqongileyo kwimeko ye-EE ngeyure nje ze-3 (okt ukubonakaliswa kukhuthazo lweenoveli ezininzi) kube neziphumo ezifanayo, ukwandisa ukubonakaliswa kohlobo lwendlela kwiindlela ezihambelana ne-neuritogenesis kunye neplityity (Rampon okqhubekayo., 2000).

Njengomvuzo womthambo, njengento eqhelekileyo ubume beplastiki obangelwa yi-EE bubonakala bunciphisa ubuntununtunu kweziyobisi zokuphathwa gadalala kwaye banokuthi babeke "indlela yokuzikhusela" ekuthatheni iziyobisi (Izitebhisi kunye neBardo, 2009; Thiel okqhubekayo, 2009; Isolinas okqhubekayo, 2010; Thiel okqhubekayo, 2011). Xa kuthelekiswa nezilwanyana ezikwiimeko ezihlwempuzekileyo, i-EE ivelise utshintsho oluchanekileyo kwindlela yokuphendula yedosi yokuqalisa ngentsholongwane ka-morphine, kunye nethonya leemphine- kunye ne-amphetamine.Bardo okqhubekayo, 1995; Bardo okqhubekayo, 1997). Imeko efanayo yaqwalaselwa emva konyango lwe-psychostimulant, apho i-EE ilandelisa ukusebenza kwe-locomotor kunye nefuthe lokwenza amandla e-nicotine kunye nokunciphisa ukuzilawula kwe-cocaine kunye nokufuna indlela yokuziphatha (nangona i-EE yanda i-cocaine yeCoca) (Luhlaza okqhubekayo, 2003; Luhlaza okqhubekayo, 2010). Into ebangela umdla kukuba i-EE ayikhange ihambise iyantlukwano kwi-NAc okanye kwi-striatal DA synthesis okanye kwi-op opateate receptor ekubambeni kwimimandla emininzi ye-mesocorticolimbic ephandwayo (Bardo okqhubekayo., 1997), nangona u-Segovia kunye noogxa bakhe bafumene ukunyuka kwesiseko kunye ne-K+-cetywe i-NAc DA kulandela i-EE (Segovia okqhubekayo., 2010). Kwi-PFC (kodwa hayi i-NAc okanye istriatum), iigundane ze-EE zifunyenwe zinciphisile umthamo wothutho lwedopamine (Zhu okqhubekayo, 2005). Oku kukonyuka kokubonakaliswa kokuqala kwe-DA kunokuchaphazela imisebenzi ye-mesolimbic, ukungafakwa, kunye nokuzilawula iziyobisi (IDutch, 1992; I-Olsen kunye neDuvauchelle, 2001, 2006; Everitt okqhubekayo., 2008; UDel Arco kunye no-Mora, 2009). Umsebenzi wamva nje uchonge umsebenzi we-CREB kunye nokunciphisa i-BDNF kwi-NAc elandelayo ye-30 kwiintsuku ze-EE ngokuthelekiswa namagundane ahlwempuzekileyo (Luhlaza okqhubekayo., 2010), nangona amanqanaba e-NAc BDNF ayefana phakathi kwe-EE nokulawula iigundane emva konyaka omnye wezindlu (Segovia okqhubekayo., 2010). I-EE ichaphazela nomsebenzi okhutshelweyo obangelwa ziziyobisi zokuxhatshazwa. Ukwenziwa kohlobo lwakuqala nje zif268 kwi-NAc yi-cocaine iyancitshiswa, njengoko kubhekiswa kwi-cocaine ye-cocaine kwi-striatum (nangona i-EE ngokwayo yafunyanwa iphakamisa i-striatal delta FosB) (Isolinas okqhubekayo, 2009). Iziphumo "zokuzikhusela" azibonwa nje kwinqanaba lokulutha. Iqondo leplastiki ebangelwa yi-EE likhulu kangangokuba liyaqhubeka ukufundwa ngokubhekisele ekukhuseleni nasekuphuculeni ukubuyiswa kwezifo zemithambo-luvo (van Praag okqhubekayo., 2000a; Iinqwelomoya kunye noHannan, 2005; INithianantharajah kunye noHannan, 2006; NguLaviola okqhubekayo, 2008; I-Lonetti okqhubekayo, 2010), kwaye ingxelo yakutshanje yaze yafumana ukonyuka okuxhomekeka kwe-hypothalamic ekuxolelweni komhlaza xa izilwanyana bezigcinwe kwi-EE (Cao okqhubekayo, 2010). Njengoko kuchaziwe malunga nokuzivocavoca, ukwenza izigqibo malunga nefuthe le-EE kulawulo lweziyobisi kufuneka kwenziwe ngelixa kuqwalaselwa iziphumo ezinokubakho zokudakumbisa kwezindlu. Njengokuzivocavoca, i-EE ibonakaliswe ukwandisa i-hippocampal neurogeneis (van Praag okqhubekayo., 2000b) kunye nokunciphisa isiphumo sokudakumba soxinzelelo kwiintonga (NguLaviola okqhubekayo., 2008).

6. Ingxoxo

Kwabanye abantu, kukho utshintsho ukusuka "kwesiqhelo" ukuya ekubandakanyekeni okunyanzelekileyo kwimivuzo yendalo (njengokutya okanye isondo), imeko abanye abathi kukuziphethe kakubi okanye ukungabikho iziyobisi (Holden, 2001; Grant okqhubekayo., 2006a). Njengoko uphando kwizifundo ezingekho iziyobisi ziqhubela phambili, ulwazi olufunyenwe kwimiba yokusetyenziswa kweziyobisi, ukuqhubela phambili, kunye nokunyanzeliswa okungafunekiyo kuya kuba negalelo kuphuhliso lwamacebo onyango kwabo bangabikho iziyobisi. Kukho ubungqina obuvela klinikhi bokuba iikhemesti ezisetyenziselwa ukunyanga iziyobisi kunokuba yindlela efanelekileyo yokunyanga iziyobisi ezingekho mthethweni. Umzekelo, i-naltrexone, i-nalmefine, i-N-acetyl-cysteine, kunye ne-modafanil zixeliwe zonke ukunciphisa umnqweno wokungcakaza kwi-pathological (kim okqhubekayo, 2001; Grant okqhubekayo, 2006b; I-Leung kunye neCottler, i-2009). Iqela elichasene ne-Opiate likwabonise isithembiso kwizifundo ezincinci kunyango lokuziphatha ngokwesondo okunyanzelekileyo (Isibonelelo kunye noKim, 2001), kunye nokukhanya ngaphezulu kubonakalise impumelelo ekunciphiseni iziqwengana zokutya kunye nobunzima kwizigulana ezityebileyo ezineengxaki zokutya kakhulu (McElroy okqhubekayo, 2007). Impumelelo yezi zonyango zokungasebenzisi iziyobisi engekazizo iziyobisi iphinda iphakamise ukuba kukho imihlathana eqhelekileyo phakathi kweziyobisi kunye neziyobisi.

Imodeli yezilwanyana ezinokunyanzeliswa nokuziphatha okunyanzelekileyo iya kunceda ukubonelela ngengqondo kwiindlela zangaphakathi ezibangelwa kukungasebenzisi iziyobisi gwenxa (Umkhuhlane, i-2009; Winstanley okqhubekayo, 2010). Ezinye iintlobo zezidakamizwa ezingezizo iziyobisi zithathwa lula ngokulula kwiintonga kunezinye. Umzekelo, i-paradigms esebenzisa ukufikelela kukutya okunezondlo ezininzi inike isikhokelo esihle sokufunda sotshintsho kukutya okunyanzelekileyo okanye okuthe gabalala. Iimpawu zodongwe ezisebenzisa ukufikelela kumanqatha aphezulu, iswekile eninzi, okanye "indlela yokutya" yakhokelela ekunyusweni kwe-caloric nokufumana ubunzima bomzimba, izinto eziphambili zokutyeba kakhulu komntu (URothwell kunye neStock, 1979, 1984; Lin okqhubekayo, 2000). Ezi ndlela zonyango zinonyusa inkuthazo yexesha elizayo kumvuzo wokutya (Wojnicki okqhubekayo, 2006) kunye nokukhokelela kwiinguqu kwi-neural plastikiity kwinkqubo ye-mesolimbic dopamine (Hoebel okqhubekayo, 2009). Iimodeli zokulawulwa kokutya zifumanise ukuba iindlela ezinxulumene nokutya kunye noxinzelelo kunokukhokelela ekubuyeleni kwakhona ekufuneni ukutya (KwiWadi okqhubekayo., 2007; Grimm okqhubekayo, 2008; UNair okqhubekayo., 2009b), into eyenzekileyo ikwenziwe ingxelo yokutyisa kwabantu (IDrewnowski, 1997; I-Berthoud, i-2004). Ke, ezi ntlobo zeemodeli zinolwazelelo oluphezulu lokwakha kwaye zinokubangela ukuba i-neuroadaptations isinike ukuqonda kwimeko yabantu njengokutya okunyanzeliswayo okanye ukuphinda ubuye kwimikhwa yokutya kakhulu kulandela utshintsho oluncedo ekutyeni.

Omnye umba wenkqubela phambili kutsha nje kukuphuhliswa kweentlobo zemodeli zokungcakaza kunye nokukhetha okuyingozi (van den Bos okqhubekayo, 2006; Imbangi okqhubekayo, 2009; I-St Onge kunye neFloresco, 2009; UZebhe okqhubekayo., 2009; I-Jentsch okqhubekayo, 2010). Izifundo zibonakalise ukuba iigundane ziyakwazi ukwenza umsebenzi wokungcakaza we-Iowa (IGT) (Imbangi okqhubekayo., 2009; UZebhe okqhubekayo., 2009) kunye nomatshini wokulalisa slot (Winstanley okqhubekayo, 2011). Olunye uphononongo lufumene ukuba iigundane ezazisebenza ngokunganyanzelekanga kwi-IGT zazinomvuzo ophakamileyo wokuziva kunye nokuthatha umngcipheko omkhuluImbangi okqhubekayo., 2009), ezifana neempawu ezinxulunyaniswe nokungcakaza kwe-pathological kunye neziyobisi kwizigulana zabantu (I-Cloninger, 1987; I-Zuckerman, 1991; ICunningham-Williams okqhubekayo, 2005; Umkhuhlane, i-2008). Usebenzisa imodeli yentonga, izifundo zikwajolise kwiindlela ezingamanyani ezingaphantsi kwe- "drive to Gamble" kunye nophuhliso lokungcakaza kwe-pathological olunokubonelela ngengqondo kuphuhliso lweesokhemesti zokungcakaza kwe-pathological (IWinstanley, 2011; Winstanley okqhubekayo., 2011).

Izifundo zobuchwephesha zisebenzisa ubuchule bokuvuselela iimvakalelo njengesixhobo sokuqinisa sifumene ngaphezulu kweendlela zemolekyuli ezizilawula ngokwazo zokuziqinisa kwezidlakudla kunye neziyobisi zokuxhatshazwa (I-Olsen kunye neWinder, 2009; Olsen okqhubekayo., 2010). Ngelixa uphando kule ndawo isebusaneni bayo, olu vavanyo kunye nolamva lwexesha elizayo lunokunika ukuqonda ngeendlela ezinokubakho zonyango kunyango lokusetyenziswa okunyanzelekileyo kwe-intanethi okanye umdlalo wevidiyo.

Ngelixa oku kunye nokunye ukuqhubela phambili kwiimodeli zokuziphatha ziqala ukusinika ukuqonda okunokubakho kwiinkqubo ezisisiseko seziyobisi ezingekho iziyobisi, kukho imiceli mngeni emininzi kunye nokusikelwa umda xa uzama ukumodarela indlela yokuziphatha. Omnye umda kukuba kwiimodeli ezininzi, akukho siphumo sibalulekileyo sokwenza izigqibo gwenxa okanye ukuzibandakanya okugqithileyo kwiindlela zokuziphatha. Umzekelo, imisebenzi yokungcakaza kwintonga isebenzisa imivuzo emincinci okanye ukonyuka kokulibaziseka phakathi kwembuyekezo ekuphenduleni kwizigqibo ezingalunganga, kodwa isilwanyana asikho emngciphekweni wokuphulukana nekhaya laso emva kokuphulukana noluhlu. Omnye umda kukuba ukubandakanyeka okugqithileyo kwiindlela zokuziphatha ezinje ngokutya okanye ukuzilawula ngokwakho kwimeko zelebhu kunokuba sisiphumo sezilwanyana ezingafikeleli kwezinye iimbuyekezo ezingezizo iziyobisi (Ahmed, 2005). Le meko ikhethekileyo icetyisiwe ukuba ibonise abantu abanobungozi emngciphekweni wabantu (Ahmed, 2005), nangona isamele i-caveat kwezi ntlobo zezifundo.

Ukuqhubeka nokufunda ngokusebenza ngokugqithileyo, ngokunyanzelwa, okanye ngokuziphatha gwenxa ekutyeni, ukungcakaza, kunye nezinye iindlela zokuziphatha ezingezizo iziyobisi kuya kuba yinto ephambili ekuqhubeleni phambili ukuqonda kwethu ngeziyobisi ezingamakhoboka iziyobisi. Iziphumo ezivela kwizifundo zangaphambi kokuba zisebenzise ezi ndlela zidityaniswa nophando kubantu ukuze zikhuthaze amachiza athi "crossover" anokuthi axhamle kweziyobisi nakwizikhobisi ezingezozamachiza.Grant okqhubekayo., 2006a; Umkhuhlane, i-2009; Frascella okqhubekayo., 2010).

Imibuzo eseleyo ye-6.1

Umbuzo omnye osalayo kukuba ngaba iinxalenye ezifanayo zee-neurons zenziwa zasebenza ngamachiza kunye nembuyekezo yendalo. Ngelixa kukho ubungqina obaneleyo bokuba kuninzi okwenzeka kwiindawo zobuchopho ezichaphazelekayo yimivuzo yendalo kunye neziyobisi zokuxhatshazwa (IGaravan okqhubekayo, 2000; Karama okqhubekayo, 2002; Umntwana okqhubekayo, 2008), kukho idatha ephikisanayo ngokubhekisele kubuninzi be-neural echaphazelekayo yimivuzo yendalo kunye neziyobisi. Urekhodo lweyunithi olulodwa oluvela kumlinganiso kunye ne-non-human prral transriatum lubonisa ukuba abantu abahlukeneyo be-neural bayabandakanyeka ngexesha lokuzilawula ngokwakho kwembuyekezo yendalo (ukutya, amanzi, kunye ne-sucrose) ngokuchasene necocaine okanye i-ethanol, nangona bekukho ukuphakama okuphezulu phakathi umvuzo ohlukileyo wendalo osetyenzisiweyo kwezi zifundo (Bowman okqhubekayo, 1996; Unonophelo okqhubekayo, 2000; Carelli, 2002; URobinson kunye noCarelli, 2008). Kukho ubungqina bokuba iziyobisi zeeklasi ezahlukileyo zibandakanya i-neuralles eyahlukileyo ngaphakathi kwenkqubo ye-mesocorticolimbic. Urekhodo lweyunithi olulodwa olusuka kwi-PFC yodidi kunye ne-NAc ye-roc-self-ehambisa i-cocaine okanye i-heroin iveze ukuba uninzi lwee-neurons zazibandakanyekile ngokwahlukeneyo ngexesha lokulindela kunye nokwexeshana lokumiliselwa (Chang okqhubekayo, 1998). Umahluko phakathi komvuzo wendalo kunye noweziyobisi unokungangqinelani, nangona kunjalo, kukho ubungqina bokuchasene noko. Ukulandela ukubonakaliswa kwexesha kwi-methamphetamine kunye namava ezesondo, kwabakho ukuhlangana okubonakalayo kwee-neurons ezenziwe ngale mivuzo emibini kwi-NAc, i-cterex ye-cterxe yangaphandle, kunye ne-basolateral amygdala (Frohmader okqhubekayo., 2010). Ke ngoko, ukuqasha abantu be-neural ngokusetyenziswa kweziyobisi ezithile zokuxhaphaza banokuthi gqolo befumana eminye yemivuzo yendalo, kodwa hayi abanye. Izifundo zexesha elizayo zisebenzisa ibhetri ebanzi ngakumbi yemivuzo yendalo kunye neziyobisi ziya kufuneka ukujongana nalo mba.

Omnye umbuzo ophakamayo kukuba kungakanani inqanaba lokuphononongwa kwembuyekezo yembuyekezo yendalo enokusinceda ukuba siqonde iziyobisi kunye nokungekho iziyobisi. Ubungqina bamva nje buveza ukuba ukuvezwa kweminye yemivuzo engeyiyo yeziyobisi kunokubeka “ukukhuselwa” kwimbuyekezo yeziyobisi. Umzekelo, iswekile kunye ne-saccharin inokunciphisa ukuzilawula kwe-cocaine kunye ne-heroin (UCarroll okqhubekayo., 1989; I-Lenoir kunye ne-Ahmed, i-2008), kwaye ezi zokuziqinisa zendalo zibonakalisiwe ukuba zikhuphe ikococaine ekukhetheni ukuzilawula kuninzi lwamagundane (Lenoir okqhubekayo., 2007; Cantin okqhubekayo., 2010). Kuhlahlelo lokuphononongwa kwezilwanyana kwizifundo zonke, uCantin okqhubekayo. uxele ukuba kuphela i-9% yeerats ekhetha i-cocaine ngaphezulu kwe-saccharin. Into enomdla kukuba eli candelo lincinci lezilwanyana limela inani labantu abachaphazeleka. Izifundo ezisebenzisa ukuzilawula kwe-cocaine zizame ukwalatha "ukuba lithobela" iigundane kusetyenziswa iikhrayitheriya ezilungisiweyo ukwenza imodeli ye-DSM-IV yokuxhomekeka kweziyobisi (UDeroche-Gamonet okqhubekayo., 2004; Belin okqhubekayo, 2009; Kasanetz okqhubekayo, 2010). Olu phononongo lufumanise ukuba malunga ~ 17-20% yezilwanyana ezizisebenzelayo i-cocaine ihlangabezana nazo zontathu iindlela, ngelixa kuqikelelwa amaxabiso okuxhomekeka kwe-cocaine ebantwini ngaphambili abachazwa kuluhlu lwamachiza ukusuka kwi-5-15% (Anthony okqhubekayo, 1994; U-O'Brien kunye no-Anthony, 2005). Ke, kuninzi lwesilwanyana iswekile kunye ne-saccharin zibonakala ngathi ziyomeleza kune-cocaine. Umbuzo onomdla omkhulu kukuba ingaba zimbalwa izilwanyana ezifumana ukuqiniswa kweziyobisi ukuba zikhethwe zimele abantu "abasesichengeni" esifaneleke ngakumbi kufundo lweziyobisi. Ke, ukuthelekisa ukuthanda izilwanyana ezizodwa ngokuchasene nemivuzo yendalo kunokuvelisa ukuqonda kwinto yokuba semngciphekweni okunxulunyaniswa neziyobisi.

Umbuzo wokugqibela kukuba ukulandela imbuyekezo yendalo kunokunceda na ukukhusela okanye ukunyanga iziyobisi. Ukuphuculwa kwendalo esingqongileyo kucetywe njengenye indlela yokuthintela kunye nokunyanga umlutha weziyobisi ngokusekwe kwizifundo zakwangaphambili kunye neziyobisi ezininzi zokuxhaphaza (Bardo okqhubekayo, 2001; Deehan okqhubekayo, 2007; Isolinas okqhubekayo, 2008; Isolinas okqhubekayo., 2010). Izifundo zamabanjwa oluntu zicebisa ukuba ukuphuculwa kwendalo esingqongileyo ngokuthi kusetyenziswe "indawo zonyango" inyani yindlela efanelekileyo yonyango yokunciphisa ulwaphulo-mthetho kunye nokusetyenziswa gwenxa kweziyobisi (Inciardi okqhubekayo, 2001; Butzin okqhubekayo, 2005). Ezi ziphumo ziyathembisa kwaye zicebisa ukuba ukuphuculwa kwendalo esingqongileyo kunokubuphucula ngokunokwenzeka i-neuroadaptations enxulumene nokusetyenziswa gwenxa kweziyobisi. Ngokufana nokucebiswa kokusingqongileyo, izifundo zifumanise ukuba umthambo unciphisa ukuzilawula ngokwakho kwaye uphinde ubuye kweziyobisi zokuxhatshazwa (Qhobosha okqhubekayo., 2002; Zlebnik okqhubekayo., 2010). Kukho obunye ubungqina bokuba ezi zinto zifunyanisiweyo ziguqulela kubantu, njengoko ukuzivocavoca kunciphisa iimpawu zokurhoxa kwaye ziphinde zibuyele kubantu abatshayayo abangahlaliyo (daniel okqhubekayo, 2006; Iprochaska okqhubekayo, 2008), kwaye inkqubo enye yokuvuselela iziyobisi ibone impumelelo kubathathi-nxaxheba abaqeqeshayo kwaye bakhuphisane kumncintiswano njengenxalenye yenkqubo (I-Butler, 2005).

7. Iingxelo eziqukumbelayo

Kukho ukufana okuninzi phakathi kweziyobisi ezingekho iziyobisi kunye neziyobisi, kubandakanya inkanuko, ulawulo olungalunganga kwindlela yokuziphatha, ukunyamezelana, ukurhoxa, kunye namazinga aphezulu okubuyela kwakhona (Amanqaku, 1990; I-Lejoyeux et al., 2000; Iziko leSizwe leSizwe ngokuSetyenziswa gwenxa kweziyobisi (NIDA) et al., 2002; Umkhuhlane, i-2006). Njengoko ndijongile, kukho ubungqina bokuba imivuzo yendalo iyakwazi ukuxhokonxa ubukho beplastiki. Oku akufanelanga ukuba kumangalise, njengoko i-1) iziyobisi zokusebenzisa gadalala zibonisa isenzo ngaphakathi kwengqondo efanayo, nangona zibhengezwa ngakumbi kunemivuzo yendalo.IKelley kunye neBerridge, 2002), kunye ne-2) ubudlelwane obufundwe phakathi kwezinto ezinje ngokutya okanye amathuba ezesondo kunye neemeko ezenza ukuba ubukho bube luncedo kumbono wokuphila kwaye ngumsebenzi wendalo wengqondo (I-Alcock, i-2005). Kwabanye abantu, oku kuxhasana ngeplastikhi kunganegalelo kwimeko yokuzibandakanya ekuziphatheni okufana nokubakho kweziyobisi. Idatha ebanzi ibonisa ukuba ukutya, ukuya ezivenkileni, ukugembula, ukudlala imidlalo yevidiyo kunye nokuchitha ixesha kwi-intanethi kukuziphatha okunokuhlakulela ekuziphatheni okunyanzelekileyo okuqhubekayo ngaphandle kokufumana iziphumo ezibi (Oselula, 1998; UTejeiro Salguero kunye noMoran, 2002; UDavis noCarter, 2009; UGarcia kunye noTibaut, 2010; I-Lejoyeux kunye ne-Weinstein, i-2010). Njengakwisiyobisi iziyobisi, kukho ixesha lotshintsho olwenziweyo ukusuka kumodareyitha ukuya ekusebenziseni ngokunyanzelekileyo (Grant okqhubekayo., 2006a), nangona kunzima ukudweba umgca phakathi “kokuqhelekileyo” kunye nokulandela ngomvuzo. Enye indlela enokubakho yokwenza lo mahluko kukuvavanya abaguli besebenzisa indlela ye-DSM yokuxhomekeka kwezinto. Sebenzisa le ndlela, iingxelo zenziwe ukuba ezi nkqubo ze-DSM zinokufezekiswa xa zisetyenziswa kwizigulana ezenza ngokunyanzelekileyo ukuba zizibandakanye nezesondo (Goodman, 1992), ukungcakaza (Umkhuhlane, i-2006), ukusetyenziswa kwe-Intanethi (I-Griffiths, i-1998), kunye nokutya (Ifland okqhubekayo, 2009). Ithathwe kwinto yokuba i-DSM-5 kulindeleke ukuba ibandakanye iindidi zokumodareyitha kunye nokubi kakhulu “kumlutha nakwimeko yokuphazamiseka” (Umbutho we-Psychiatric Association, i-2010), mhlawumbi inokusebenzela abaphandi abaphazamisiyo kunye noochwephesha ukuba baqwalasele ubugqirha njengesiphene. Kweminye imimandla, olu hlobo lokwenza amagama lwancede ukukhulisa ulwazi lokuba iingxaki ezinje nge-autism kunye notywala obunxilisayo kumanqanaba obunzima. Kwimeko yotywala (iziyobisi okanye olungelulo iziyobisi), ukuphawulwa kweempawu kwanaphantsi komgangatho 'wokumodareyitha' kunokunceda ukubona umntu osengozini kwaye uvumele ungenelelo olusebenzayo. Izifundo ezizayo ziya kuqhubeka nokubonisa ukuqonda ngendlela yokufumana ukunyanzelwa kwembuyekezo yendalo kunokuba yinto enyanzelekileyo kwabanye abantu nendlela elungileyo yokunyanga iziyobisi ezinganakho iziyobisi.

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1 Table          

Isishwankathelo sePlatinity Ejongiweyo ukulandela ukuBhengeza iziyobisi okanye abaThengisi bendalo.

Imibulelo

Inkxaso yemali yanikezelwa yi-NIH isibonelelo DA026994. Ndingathanda ukubulela uKelly Conrad, Ph.D. kunye noTiffany Wills, Ph.D. ukwenza amagqabantshintshi awakhayo kwiinguqulelo zangaphambili zalo mbhalo obhaliweyo.

Imihlathi

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

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