Boikarabello ba meriana ea boitšoaro ba boitšoaro bo khethollang boiteko: dopamine, adenosine le ho feta (2012)

J Exp Anal Behav. 2012 Jan;97(1):125-46. doi: 10.1901/jeab.2012.97-125.

Salamone JD1, Correa M, Nunes EJ, Randall PA, Pardo M.

inahaneloang

Ka lilemo tse ngata, ho 'nile ha boleloa hore lithethefatsi tse sitisang phetiso ea dopamine (DA) li fetola "phello" e matlafatsang ea lithuso tse kholo tse kang lijo. Patlisiso le mohopolo o amanang le mesebetsi ea DA ea maiketsetso li ntse li hlophisoa bocha, ka moetlo o hatelletseng hedonia le moputso oa mantlha o hlahisang likhopolo le mela e meng ea lipatlisiso. Tlhatlhobo ea hajoale e shebane le ho nka karolo ha nucleus accumbens DA ka boits'oaro bo amanang le boiteko. E shebiloe ho latela moralo oa moruo oa boits'oaro, litlamorao tsa ho bokella ho felloa ke matla ha DA le ho hanyetsa boits'oaro bo matlafalitsoeng ke lijo ho its'etlehile holima litlhoko tsa mosebetsi oa seletsa, 'me likhoto tse felisitsoeng ke DA li bonts'a kutloisiso e phahameng ea litšenyehelo tsa karabelo, haholoholo litlhoko tsa karolelano. Ho feta moo, ho kena-kenana le ho bokella phetisetso ea DA ho na le tšusumetso e matla holim'a boits'oaro bo amanang le boiteko. Likhoto tse nang le pokello ea ho felloa ke matla ea DA kapa khanyetsano li fetisetsa boits'oaro ba bona hole le mesebetsi e matlafatsoang ke lijo e nang le litlhokahalo tse phahameng tsa karabelo, hape e bonts'a khetho e eketsehileng ea likhetho tse tlase tsa matlafatso / theko e tlase. Nucleus accumbens DA le adenosine lia sebelisana ho laola mesebetsi e amanang le boiteko, le likarolo tse ling tsa boko (anterior cingulate cortex, amygdala, ventral pallidum) le tsona lia ameha. Liphuputso tsa litsamaiso tsa boko tse laolang ts'ebetso e sebetsanang le boiteko li kanna tsa ba le moelelo oa ho utloisisa tšebeliso e mpe ea lithethefatsi, hammoho le matšoao a kang psychomotor slowing, mokhathala kapa anergia ho tepella maikutlong le mathata a mang a methapo.

Keywords: dopamine, adenosine, boiteko, mosebetsi, matlafatso, moruo oa boitšoaro, tlhahlobo

Bakeng sa ho phela, libopuoa li tlameha ho fihlella mohopolong oa bohlokoa o kang lijo, metsi, thobalano le maemo a mang. Lits'ebetso tse kenyellelitsoeng liketsong tse joalo tsa boits'oaro li fapana ebile li rarahane, 'me mohopolo oa boko o amanang le lits'ebetso tsena ke taba ea ho etsa lipatlisiso tse ngata. Lits'ebetso tsa ho ithuta tsa thulusi tse kenyelletsang matlafatso le kotlo li lebisa ho fumanoeng hoa boitšoaro bo laolang monyetla oa ho ba haufi, ho ba haufi le ho ba le ts'usumetso ea bohlokoa. Empa leha likarabo tse joalo li se li fumanehile, lintlha tse ngata li tlatsetsa ho khethoeng ha boits'oaro bo itseng ba sebopeho tikolohong e fanoeng ea tikoloho. Mohlala, tikolohong e rarahaneng, likokoana-hloko li na le phihlello ea mefuta-futa e mengata, e ka fapana ka boleng ba tsona, bongata le sebopeho sa nakoana. Ntle le moo, liketso tse ikhethang tse sebetsang li ka amahanngoa le bathusi ba itseng, 'me liketso tsena li ka fapana haholo ho topography le ho latela likarolo tsa litlhoko tsa karabelo. Likarolo tse 'maloa tsa patlisiso ho saense ea boits'oaro, ho kenyelletsa le lipatlisiso mabapi le karabelo ea matlafatso ea karabelo, khopolo e nepahetseng ea ho qala, le moruo oa boitšoaro, li hlahile e le ho tšoaea boitšoaro bo khethiloeng bo bonoang libakeng tsena tse rarahaneng (Allison, 1981, 1993; Aparicio, 2001, 2007; Baum, 1974; Hengeveld, van Langevelde, Groen, & de Knegt, 2009; Hursh, Raslear, Shurtleff, Bauman, & Simmons, 1988; Madden, Bickel, & Jacobs, 2000; Madden le Kalman, 2010; Salamone, 1987; Tustin, 1995; Vuchinich le Heather, 2003; Williams, 1988). Patlisiso ena e fane ka mekhoa ea ho utloisisa hore na boleng ba matlafatso, hammoho le litlhoko tsa karabo, bo susumetsa kabo ea boleng bo tšoanang ba litso tse ngata tse fapaneng.

Sengoloa sena sa maikutlo se tla fana ka kakaretso ea lipatlisiso tsa morao-rao mabapi le boikoetliso ba meriana mabapi le tšibollo ea karolo e itseng ea litaba tsena tse pharaletseng. Ntlha e 'ngoe e amanang le karabo e susumetsang ka matla boitšoaro ba lits'ebetso ke litjeo tsa karabelo tse amanang le mosebetsi (Foltin 1991; Hursh et al., 1988; Kaufman 1980; Kaufman, Collier, Hill, & Collins, 1980; Madden et al., 2000; Salamone, 1986, 1987, 1992; Staddon 1979; Tustin, 1995). Tlhahlobo ea hona joale e tla shebisisa litlamorao tsa lithethefatsi le bokhoba ba methapo ea methapo bo amang phetisetso ea dopamine (DA), le hore na litlamorao tsena li sebetsana joang le litlhoko tsa karabelo, haholo-holo litlhoko tsa tekanyetso, tse behiloeng ho ts'ebetso e matlafalitsoeng ea lijo. Ntle le moo, sengoloa se tla lekola lingoliloeng ka karolo ea DA maemong a boikhethelo a amanang le boiteko, ka ho totobatsa e le DA sebakeng sa boko se tsejoang ka hore ke li-nucleus accumbens. Kamora nako, ho tla buisanoa ka tšebelisano-'mano lipakeng tsa li-nucleus tse bokellanang DA le li-neurotransmitters le libaka tsa boko, 'me ho tla nahanoa ka botebo bo amanang le liphetho tsena.

LITLHOHONOLOFATSO TSE BOTSOANG HYPOTHESISE TSA AN ANONONISTS: LITLHAKISO TSA TLHOKOMELISO LE TSOALO EA "MOTSOALLE" HYPOTHESIS EA DA FUNCTION

Ho bile le nts'etsopele ea bohlokoa theoretical lilemong tse 'maloa tse fetileng tse amanang le ts'ebetso ea boitšoaro ea hypothesised ea DA, haholo-holo li-nucleus li bokella DA. Bakeng sa ho nahana ka ho nka karolo ha DA ho likarolo tse amanang le kabo ea karabo ea bohloka, motho o lokela ho beha mehopolo ena ho nalane ea nalane le mesebetsi e meng e amanang le DA. Mashomeng a lilemo a seng makae a fetileng, e ile ea e-ba ntho e tloaelehileng ho lingoliloeng tsa "neuroscience" ho bitsa DA e le "moputso" oa ho fetisetsa litaba, o neng o boleloa o hlahisa maikutlo a thabo e nyane kapa litabatabelo tsa takatso tse matlafatsang kapa tse tsamaisang liketsahalo tse matlafatsang. Leha ho le joalo, ho bonahetse ho bafuputsi ba bangata hore ho na le meeli e hlakileng le mathata a tlisoang ke polelo ea setso ea "moputso" oa DA (Baldo & Kelley, 2007; Barbano le Cador 2007; Salamone, Correa, Farrar, & Mingote, 2007; Salamone, Correa, Farrar, Nunes, & Collins, 2010; Salamone, Correa, Mingote, & Weber, 2005; Salamone, Metsoala, & Snyder, 1997; Salamone, et al., 2009), eseng boholo ba eona ke tšebeliso ea lentsoe "moputso" ka boeona (Cannon & Bseikri 2004; Salamone 2006; Salamone et al. 2005; Sanchis-Segura le Spanagel, 2006; Yin, Ostlund, & Balleine, 2008). Poleloana "moputso" ha e hlalosoe hangata ke bafuputsi ha ba e sebelisa ho hlalosa mokhoa oa boitšoaro. Ba bang ba sebelisa lentsoe lena joalo ka ha eka ke lentsoe le tšoanang le "matlafatsa", ha ba bang bona ba le sebelisa ho bolela "takatso ea lijo" kapa "tšusumetso ea mantlha". Ba bang hape ba sebelisa poleloana ena e le lebitso le koaheletsoeng ka lesira ka "thabo". Maemong a mangata, lentsoe "moputso" ho bonahala le sebelisoa e le poleloana e le 'ngoe e akaretsang lefats'e ka bophara ho likarolo tsohle tsa ho matlafatsa thuto, khothatso le maikutlo, ekaba li maemong kapa ha li na liphoso. Haeba e sebelisoa ka mokhoa ona, moputso oa lentsoe o pharaletse hoo ho se nang thuso. Ho lokela ho totobala hore ho thata ho hlahloba mohopolo o tšehetsang hore neurotransmitter e sebelisana le lits'ebetso tse joalo tse sa hlalosoang hantle. Kahoo, ho fanoe ka maikutlo a hore ho molemo ho boloka phapang pakeng tsa moputso le matlafatso; ka ts'ebeliso ena, matlafatso e bua ka kotloloho ho mekhoa ea ho ithuta ea bohlokoa (Sanchis-Segura le Spanagel, 2006; 2004 e Bohlale), ha moputso o batla o kenyelletsa sephetho sa mantlha sa maikutlo le maikutlo a ho matlafatsa maikutlo (Everitt le Robbins, 2005; Salamone et al., 2005, 2007).

Ntle le litaba tsena tse nang le 'nete' me li na le 'nete, ho boetse ho na le bopaki bo matla bo bokelletsoeng lilemong tsa morao tjena, bo sa atleheng ho ts'ehetsa mefuta e fapa-fapaneng ea mehopolo ea DA ea "moputso". Taba e 'ngoe e makatsang ke hore lits'ebetso tse amanang ka kotloloho le tšebeliso ea moputso oa mantsoe (ke hore, thabo ea boikhethelo, tšusumetso e kholo) ke tse bonts'itsoeng li le bothata haholo ho latela ho bonts'a ho kenya letsoho ha lits'ebetso tsa DA (Salamone et al., 2007). Mohlala, mohopolo oa hore li-nucleus li bokella DA o buella thabo e tlalehiloeng ka mokhoa o hlakileng e amanang le tšehetso e ntle e hlahisitsoe ke phephetso e matla (Berridge, 2007; Berridge le Kringlebach, 2008; Salamone et al., 2007). Ho kena-kenana le phetisetso ea DA ha ho senye monyetla oa tatso ea monate oa takatso bakeng sa sucrose (Berridge, 2007; Berridge le Kringlebach, 2008), e leng lets'oao la boitšoaro le sebelisoang khafetsa ho reaction ea hedonic ka litoeba. Liphuputso tsa batho li tlalehiloe hore bahanyetsi ba DA ba sitiloe ho bua ka mokhoa o ikhethileng o hlahisitsoeng ke lithethefatsi tsa tlhekefetso (Brauer & de Wit, 1997; Gawin, 1986; Haney, Ward, Foltin, & Fischman, 2001; Nann-Vernotica, Donny, Bigelow, le Walsh, 2001; Venugopalan et al., 2011; Wachtel, Ortengren, & de Wit, 2002).

Ntle le moo, karolo e ka bang teng ea litsamaiso tsa DA ho boits'oaro bo matla kapa ho ithuta ha e felle feela maemong a kenyang matlafatso e ntle. Ho na le bopaki bo bongata ba hore metheo ea litoro ka kakaretso, le li-nucleus li bokella DA ka kotloloho, hape e nka karolo likarolo tsa ho ithuta ho sa khaotseng, kotlo, le karabelo molemong oa boiphetetso (Blazquez, Fujii, Kojima, & Graybiel, 2002; Delgado, Li, Schiller, & Phelps, 2008; Ho felloa ke matla, Reynolds, Richard, & Berridge, 2008; Martinez, Oliveira, Macedo, Molina, & Brandao, 2008; Munro le Kokkinidis, 1997; Salamone, 1994). Leha lithuto tsa monahano oa batho li sebelisoa ho ts'ehetsa mohopolo oa hore li-nucleus li bokella thabo ea subjective (mohlala Sarchiapone et al., 2006), maemo a rarahane ho feta (Pizzagalli, 2010); ka sebele lipatlisiso tse sebelisang mekhoa e fapaneng ea ho nahana li bontšitse hore methapo ea kutlo ea motho le eona e sebetsana le khatello ea maikutlo, ho ferekanya le ho ferekanya kelello (Delgado et al., 2008; Delgado, Jou, & Phelps, 2011; Jensen et al., 2003; Levita et al., 2009; Liberzon et al., 1999; Pavic, 2003; Phan et al., 2004; Pruessner, Champagne, Meaney, & Dagher, 2004). Lithuto tsa Neurochemical le physiological ho liphoofolo li bontša ka ho hlaka hore ts'ebetso ea neuron ea DA ha e tlangoe feela ke ho tlisoa ha li-reinforcers tse ntle tsa mantlha. Lithutong tse kenyelletsang matlafatso ea lijo liphoofolong tse koetlisitsoeng, keketseho ea ho lokolloa ha DA e ne e amana haholo le karabelo ea bohlasoa, kapa tšusumetso ea boemo bo tiisang phumaneho ea matlafatso, ho fapana le ho fana ka ts'ebeletso (Roitman, Stuber, Phillips, Wightman, & Carelli, 2004; Segovia, Correa le Salamone, 2011; Sokolowski, Conlan, & Salamone, 1998). Ho feta moo, ts'ebetso ea neuron ea DA le ho lokolloa ha DA li ka kenngoa tšebetsong tse fapaneng tse fapaneng (mohlala, footshock, tailshock, mohatla o tsitsitseng, khatello ea maikutlo, maemo a hlohlontšang maikutlo, litla-morao tse hlolang khatello ea maikutlo, maemo a khatello ea sechaba) le maemo a ho rata (Anstrom & Woodward 2005; Brischoux, Chakraborty, Brierley, & Ungless, 2009; Lefielo le Yamamoto 2005; Guarraci & Kapp 1999; Marinelli, Pascucci, Bernardi, Puglisi-Allegra, & Mercuri, 2005; McCullough le Salamone, 1992; McCullough, Sokolowski, & Salamone, 1993; Schultz 2007a, 2007b; E monyenyane, 2004). Liphetoho tsena tsa methapo ea kutlo li bonoa nakong tse fapaneng tse fapaneng tsa nako (ho kenyeletsa le liphetoho tse potlakileng tsa phasic le phasic tse potlakileng; Hauber 2010; Roitman et al., 2004; Salamone 1996; Salamone et al. 2007; Schultz 2007a, 2007b; Segovia et al., 2011). Lipatlisiso tsa ho ithuta li bonts'a hore litsamaiso tsa DA ka kakaretso le li-nucleus ka ho khetheha ha li amehe feela ho ithuteng tse amanang le matlafatso (mohlala. Bohlale, 2004), empa hape ba nka karolo ho ithuteng ho amanang le kotlo (Salamone et al., 2007; Schoenbaum & Setlow, 2003). Kahoo, ho fanoe ka maikutlo a hore lentsoe "ho ithuta ka matla" le ka sebelisoa haholo ho feta "ho matlafatsa ho ithuta" bakeng sa ho hlalosa karolo e kholo ea karolo ea DA lits'ebetsong tsa ho ithuta (Salamone et al., 2007).

Haeba khang ea DA e hlile e kena-kenana le litšobotsi tsa mantlha tsa ho matlafatsa maikutlo, sena se etsa hore motho a botse hore na litšobotsi tseo ke life. Ehlile, matlafatso a bua ka maemo a ts'ohanyetso a ts'ebetso a nkang ho matlafatsa boitšoaro bo itseng; Matlafatso ea ts'ebetso e bolela ts'ebetso eo karabo e lateloang ke tlhahiso ea khothatso eo hangata e lumellanang karabong eo, mme liketsahalo tsena li lateloa ke keketseho ea monyetla oa ho hlaha hoa karabelo nakong e tlang. Leha ho le joalo, ho bohlokoa ho nahana ka hore na ke thepa efe e thusang mothetsi ho sebetsa joalo ka matlafatso. Joalokaha ho hlokomeloa khafetsa, Skinner o ne a sa bue hangata khafetsa ka litšobotsi tsa bohlokoa tsa susumetso tse ba lumellang ho sebetsa e le bathusi. Le ha ho le joalo, Skinner o kile a nahana ka karolo ea lipapatso tse kang ho haelloa ke lijo mosebetsing oa ho matlafatsa. Ka mohlala, Skinner (1953) e boletse "Matlafatso ka hona a tlisa boits'oaro tlasa taolo ea bohloki bo loketseng. Kamora hore re lokise leeba hore le otlolle molala oa lona ka ho le matlafatsa ka lijo, se fapaneng se laolang ho otlolla molala ke khaello ea lijo ”(leq. 149). Bafuputsi ba bang ba bangata ba fane ka maikutlo a bona ka taba ena, mme ho 'nile ha boleloa hore ho na le litšobotsi tse tloaelehileng tse hlakileng libakeng tse fapaneng tsa lipatlisiso (Salamone le Correa, 2002). Palo e kholo ea bafuputsi ba ngotseng ka litšobotsi tsa mantlha tsa ho matlafatsa maikutlo ba fihlile qeto ea hore lintlha tse khothatsang hangata li ratoa, kapa ho phahamisa boitšoaro, le hore litlamorao tsena ke karolo ea motheo ea ts'usumetso e ntle. . Ka mohlala, Tapp (1969) e itse “boemong bo bonolo ka ho fetisisa, batšehetsi ba na le matla a ho tataisa boitšoaro ba sebopuoa. Lits'usumetso tseo ho atamelanoang le tsona li nkuoa e le tse matlafatsang "(leq. 173) Li-reinforcers li 'nile tsa hlalosoa e le thepa e batloang, kapa tšusumetso e ntseng e atameloa, ea itlhokomela, ea fihlelleha kapa ea bolokoa; hape li hlalositsoe e le mesebetsi e ratoang, e amohuoang kapa e laoloa ka tsela e itseng (Dickenson le Balleine, 1994; Hursh et al., 1988; Lea, 1978; Premack, 1959; Staddon & Ettinger, 1989; Timberlake, 1993; Tustin, 1995; bona puisano ea "khothatso e khothatsang ea molao o matla oa tšebetso" ho Salamone & Correa, 2002). Ho latela tlhahlobo ea moruo ea boits'oaro e fanoang ke Hursh (1993) "Ho arabela ho nkuoa e le sekhahla se fapaneng se itšetlehileng ka sona hobane se bohlokoa ho laoleng ts'ebeliso" (leq. 166).

Bakeng sa mabaka ana, ho bohlokoa ho hlokomela hore litekanyetso tse tlase tsa bahanyetsi ba DA tse hatellang ts'ebetso ea ts'ebeliso ea matla ea lijo hangata li bontšitsoe ho tlohela boits'oaro bo lebisitsoeng ho fihlellong le tšebeliso ea lijo (Salamone et al., 1991); mananeo ana a na le phello e fokolang kenyelletsong ea lijo (Fibiger, Carter, & Phillips, 1976; Ikemoto le Panksepp, 1996; Rolls et al., 1974; Rusk & Cooper, 1994; Salamone et al., 1991), khethollo le khethollo li thehiloe holim'a boholo ba matlafatso ea lijo (Martin-Iverson, Wilke, & Fibiger, 1987; Salamone, Metsoala, & Bucher, 1994), le likarabo tse bonolo tsa mokhoa o matlafatsoang ke phepelo ea lijo (Salamone 1986). Leha ho tsebahala hore ho tlosoa hohle ha DA ka mahlakoreng ho ka hlahisa litsgia (ke hore, khaello ea ho ja), ke litsi tsa DA libakeng tse amanang le sensorimotor le libakeng tse amanang le koloi tsa morao-rao kapa tsa polokelo ea metsi tsa morao-rao tse amanang haholo le phello ena. ho e-na le li-nucleusDunnett le Iversen 1982; Salamone, JD, Mahan, K., & Rogers, S., 1993; Ungerstedt, 1971). Ka lehlakoreng le leng, li-nucleus li bokella bofokoli ba DA le bohanyetsi li bontšitsoe khafetsa hore li se ke tsa senya ts'ebeliso ea lijo haholo (Bakshi & Kelley 1991; Baldo, Sadeghian, Basso, & Kelley, 2002; Kelley, Baldo, Pratt, & Will, 2005; Koob, Riley, Smith, & Robbins, 1978; Salamone, Mahon et al., 1993; Ungerstedt 1971). Ho feta moo, litlamorao tsa ho hlaseloa ke DA kapa ho ikopanya le litlatsetso tsa DA ka ts'ebeliso ea lijo tse matlafatsoang ha li tšoane hantle le litlamorao tsa lithethefatsi tsa pele ho lijo kapa takatso ea khatello.Aberman & Salamone, 1999; Salamone, Arizzi, Sandoval, Cervone, le Aberman, 2002; Salamone et al., 1991; Ho teba, Vemuri, Olszewska, Makriyannis, & Salamone, 2008). Kahoo, likarolo tsa motheo tsa matlafatso ea mantlha le tšusumetso ea ho fumana phihlello li lula li tsitsitse kamora ho hlaseloa ke DA kapa ho bokelloa ha DA.

Leha ho fanoe ka tlhahiso ea hore liketso tse amanang le moputso tsa litekanyetso tse tlase tsa bahanyetsi ba DA kapa li-nucleus tse bokellanang ho tlosoa ha DA li lokela ho hlahisa litlamorao tse tšoanang hantle le ho timela. Beninger et al., 1987; Bohlale, Spindler, de Wit, & Gerberg, 1978), ho na le mathata a 'maloa ka monahano ona. Le ha karolo e kahare e hana ho arabela ka ho susumetsoa ke bahanyetsi ba DA ho thoe ke "phethello", litlamorao tse ts'oanang li bonoa ho matšoao a koloi a parkinsonism. Haase & Janssen (1985) e hlokometse hore micrographia e bonts'itsoeng ke bakuli ba nang le neuroleptic-induced parkinsonism e tšoauoa ka ho mpefala ho hoholo nakong ea sengoloa. Ba boletse hore "Sekhahla se ntseng se eketseha sa ho fokotsa mongolo ho tloha sethaleng ho isa setulong se tsebahala haholo, 'me maemong a tloaelehileng sebaka se koahetsoeng ke mongolo se nka sebopeho sa piramite e khelohileng" (p 43). Bangoli bana ba boetse ba tlaleha hore matla a ho tlanya menoana ka kakaretso a fokotseha nakong ea setulo ho bakuli ba nang le neuroleptic-induced parkinsonism (leq. 234). Ka mokhoa o ts'oanang, bakuli ba parkinsonia ba ntseng ba hatella matsoho khafetsa ba bontša ho fokotsa butle-butle tlhahiso ea makoloiSchwab, 1972). Litekong, bahanyetsi ba DA ba baka tlatsetso ea nako e telele molemong oa karabelo (Liao & Fowler, 1990), le ka nako ea thuto e fokotsehile ka matla a likhama (Das & Fowler, 1996) le boitšisinyo (Pitts & Horvitz, 2000). Ntle le moo, taolo e pheta-phetoang ea bahanyetsi ba DA ho likhoto e lebisa tlhokomatsong e ikhethileng ea karabelo ea catalepsy ka linako tsohle (Amtage & Schmidt, 2003). Ntle le moo, liphuputso tse 'maloa li bapisitse ka ho toba litlamorao tsa khanyetsano ea DA le ho timela,' me li bontšitse phapang e kholo lipakeng tsa maemo ana (Asin & Fibiger, 1984; Evenden le Robbins, ka 1983; Faustman le Fowler, 1981, 1982; Feldon & Winer, 1991; Grling, Fowler, & Collins, 1984; Grling, Fowler, & Tizzano, 1987; Rick, Horvitz, & Balsame, 2006; Salamone 1986; Salamone, Kurth, McCullough, & Sokolowski, 1995, Salamone, et al., 1997; Spivak & Amit, 1986; Willner, Chawala, Sampson, Sophokleous, & Muscat, 1988; Wirtschafter le Asin, 1985). Mohlala, Evenden & Robbins ba bonts'itse litekanyo tse tlase tsa α-flupenthixol (0.33-0.66 mg / kg) e fokotsitseng sekhahla sa karabelo ha ea ka ea hlahisa litlamorao tse neng li tšoana le ho fela ha likhoto tse arabang mosebetsi oa win-stay / lose-shift. Rick le al. e tlaleha hore ho felloa ke matla ho ile ha eketsa phapang ea boitšoaro ho likhoto tse koetliselitsoeng mosebetsi oa bohlokoa, ha tekanyetso e tlase ea mohanyetsi oa D1 SCH 23390 kapa D2 antagonist raclopride e sa ka ea etsa joalo.

Mohlala o mong o tsoang ho lingoliloeng tsena ke Salamone (1986), e tlalehileng hore litlamorao tsa 0.1 mg / kg ea mohanyetsi oa DA haloperidol li fapane haholo le litlamorao tsa ho fela ha likhoto tse arabang ka karolelano e sa fetoheng (FR) 20 ea matlafatso. Tlas'a pheliso, likhoto li ile tsa arabela ka sekhahla se phahameng qalong ea seboka ho feta likhoto tse tšoaroang ka haloperidol, e bontšang hore likhoto tse tšoaroang ke haloperidol ha li bontše "ho phatloha ho felile" (bona hape Salamone et al., 2005, e bonts'itseng hore likhoto tse nang le deplete tsa DA li hlile li qala ho araba butle butle qalong ea seboka, ho fapana le litlamorao tsa ho timela). Ho feta moo, likhoto tse pepesitsoeng ho timela li kentse ka mokhoa o lekanang tekanyo e neng e potlakile ho feta tekanyo ea karabelo ea mantlha ea mantlha ha e bapisoa le liphoofolo tse tšoaroang haloperidol (Salamone, 1986). Teko e ngoe e bonts'itse hore, ho fapana le litlamorao tsa 0.1 mg / kg haloperidol ho FR 20 e arabelang, tekanyetso makhetlo a mane boholo boo ha e na tšusumetso karabong e matlafalitsoeng ea ho ba haufi le sejana sa lijo ka nako e sa lekanyetsoang ea 30 sec kemiso (Salamone, 1986). Ho hloka matla ha bohanyetsi ba DA karabong ena e bonolo e matlafatsoang ke lijo ho eme hole le phello ea ho timela, e ileng ea hatella karabelo e matla. Thutong eona e le 'ngoe, ts'ebetso ea sepheo sa tšusumetso ea kemiso e hlophisitsoeng e boetse e tlalehiloe ka ho tšoana le karabelo ea bohlokoa ea ho ba haufi le sejana sa lijo. Joalokaha ho bonts'itsoe karolong e kaholimo ea Setšoantšo sa 1, 0.4 mg / kg haloperidol e hatelletse ts'ebetso ea makoloi e bakoang ke tlhahiso ea lijo e reriloeng empa, joalo ka ha ho bonts'itsoe karolong e ka tlase, haloperidol ha ea ka ea ama karabelo e matlafalitsoeng. Hammoho le lithuto tse ling, liphetho tsena li totobatsa likarolo tse 'maloa tsa bohlokoa tsa litlamorao tsa bora ba DA. Taba ea mantlha, litlamorao tsa lehloeo la DA ha li tšoane hantle le litlamorao tsa ho timela maemong a fapaneng (Salamone et al., 1997). Taba ea bobeli, bohanyetsi ba DA bo ile ba hatella tšebetso ea makoloi ea kemiso e hlophisitsoeng; lithuto tsa boits'oaro li bonts'itse hore ho fana ka kemiso e reriloeng ea li-reinforcers ho ka ba le thepa e sebetsang (Killeen, 1975; Killeen, Hanson, & Osborne, 1978), mme bopaki bo bonts'ang bo bonts'a hore ho hanyetsana ha DA le ho bokella ho tlosoa ha DA ho ka fokotsa mesebetsi e thehiloeng kemisong (McCullough le Salamone, 1992; Robbins le Everitt, 2007; Robbins le Koob, 1980; Robbins, Roberts, & Koob, 1983; Salamone 1988; Wallace, Singer, Finlay, & Gibson, 1983). Qetellong, liphetho tsena li ne li lumellana le 'mele o ntseng o hola oa bopaki bo bonts'ang hore litlamorao tsa bahanyetsi ba DA ho boits'oaro ba ts'ebelisano li sebelisana ka matla le tlhoko ea karabelo ea mohopolo, le hore mekhoa e meng e matlafalitsoeng ha e ananele ke khanyetsano ea DA (Ettenberg et al., 1981; Mekarski, 1988).

Setšoantšo sa 1  

Palo ena e huleloa motheong oa data ho tsoa ho Salamone (1986). Likhoto li ile tsa lekoa ka phapusing e kholo ea tšebetso, 'me tsa matlafatsoa ka li-pellets tsa lijo tsa 45 mg lenaneong la li-FI-30 sec ho ba mokatong o ka pela sejana sa lijo. Locomotor ...

LITLHOHONOLOFATSO TSA AN ANONONISM LE HO FUMANA LITLHAKISO TSA BOPHELO TSA DAFA LE LITLHAKISO TSA BOPHELO

Tumellanong le liketsahalo tsa nalane tse hlalositsoeng kaholimo ho tloha li-1970 ho ea li-1990, ho bile le khatello ea maikutlo lithutong tsa boitšoaro mabapi le boiteko, litšenyehelo tsa karabelo kapa mathata, le meetso ea moruo ea boits'oaro. Bafuputsi ba 'maloa ba ile ba totobatsa hore na litšenyehelo kapa litšitiso tsa karabo li amme phello ea karabelo ea mohiruoa joang (Foltin 1991; Kaufman 1980; Kaufman et al. 1980; Staddon 1979; Tustin, 1995). Litlhokahalo tsa mosebetsi, joalo ka palo ea mechine ea khatiso ea lever e hlokahalang bakeng sa ho fumana lijo, li bonts'itsoe ho sebetsa e le mokhoa oa tlhahiso ea lisebelisoa tsa ts'ebetso le ho ama ts'ebeliso ea lijo (Collier & Jennings, 1969; Johnson le Collier 1987). Mehlala ea moruo oa boitšoaro e hatisa hore na lintlha tse 'maloa, ho sa kenyeletsoe boleng ba matlafatso feela, empa le maemo a amanang le litšobotsi tsa karabelo ea sesebelisoa, a ka khetholla phello ea boitšoaro (Allison, 1981, 1993; Bickel, Marsch, le Carroll, 2000; Lea, 1978). Hursh et al. (1988) o khothalelitse hore theko ea matlafatso ea lijo e le theko / karolelano ea melemo e hlalositsoeng ha boiteko bo felletsoe ka karolo ka 'ngoe ea boleng ba lijo bo felisitsoeng.

Ho na le bopaki bo bongata ba bopaki bo thusitseng ho matlafatsa tšehetso ea maikutlo a hore litlamorao tsa ho kena-kenana le phetiso ea DA li sebelisana ka matla le tlhoko ea karabelo e matla. E 'ngoe ea litsela tsa ho laola litlhoko tsa mosebetsi lenaneong la ts'ebetso ke ho sebelisa linako tse fapaneng tsa karolelano. Caul le Brindle (2001) o hlokometse hore litlamorao tsa haloperidol ea mohanyetsi oa DA mabapi le boitšoaro bo matlafatsoang ke lijo li ne li its'etleha hodima tlhoko ea karolelano, ka kemiso ea FR 1 e sa utloisisehe ho feta tekanyo e tsoelang pele. Motho a ka tlatsa putbens ea DA ka liente tsa lehae tsa ntho e amanang le neuroto tse kang 6-hydroxydopamine, 'me lithuto tse' maloa li sebelisitse mokhoa ona. Aberman le Salamone (1999) o hirile mefuta e fapaneng ea li-ratio (FR 1, 4, 16 le 64) ho lekola litlamorao tsa ho putlama ha DA. Le ha ts'ebetso ea FR 1 e sa ka ea angoa ke ho nyahama ha DA (bona hape Ishiwari, Weber, Mingote, Correa, & Salamone, 2004), mme ho arabela ha FR 4 ho bonts'itse khatello e fokolang feela le ea nakoana, li-schedule tsa FR 16 le FR 64 li ne li senyehile haholo. Mokhoa ona o bonts'itse hore ho bokelloa ha depo ea DA ho khothalelitse ho kenngoa ha maemo a boima; ke hore, likhoto tse nang le deplete tsa DA li ne li tebile haholo ho latela boholo ba tlhoko. Mokhoa ona o ka hlalosoa o bonts'a keketseho ea lebelo la tlhoko ea matlafatso ea lijo (Aberman le Salamone 1999; Salamone et al., 1997, 2009). Haeba tlhoko ea karolelano e khahla ho theko ea lihlahisoa (li-pellets tsa ho matlafatsa), ho bonahala hore likhoto tse nang le lipokello tsa DA li tebile ho feta liphoofolo tse laoloang ho theko ea lihlahisoa tsa lijo (Setšoantšo sa 2). Ha ho potelle hore, likhoto ha li sebelise chelete ho reka li-pellets tse sebetsang. Sebakeng seo, ho fanoe ka tlhahiso ea hore ts'ebetso ea ts'ebetso ke ts'ebetso ea barter, eo ho eona rat e etsang mosebetsi oa eona (kapa phokotso ea boikhathollo) bakeng sa thepa (Rachlin, 2003; Tustin, 1995). Kahoo, likhoto tse nang le li-depbenions tsa DA li tebile ho feta liphoofolo tse laolang litšenyehelo tsa karabelo tse amanang le mosebetsi, hape li na le menyetla e fokolang ea ho rekisa lijo tse phahameng. Teko e latelang, Salamone, Wisniecki, Carlson, le Correa (2001) e tlaleha hore kutloelo-bohloko e eketsehang bakeng sa litlhoko tse kholo tsa litekanyo tse nang le lipokelletso tsa DA li ile tsa bonoa ha likhoto li ne li lekoa maemong ohle a pharalletseng (a phahameng joaloka FR300), leha kamano e akaretsang pakeng tsa khatello ea lever le lijo tse hlahisoang ke mochine oa lever li bolokiloe khafetsa (ke hore, theko ea unit ea 50: FR 50 bakeng sa pellet e le 'ngoe; FR 100 bakeng sa li-pellets tse peli; FR 200 bakeng sa li-pellets tse' ne; le FR 600 bakeng sa li-pellets tse tšeletseng). Liphetho tsena li bonts'a hore boholo le tlhophiso ea tlhoko ea tekanyo li bonahala e le liphetho tse tebileng tsa kutloisiso ea kemiso ea ts'ebetso ho litlamorao tsa depbens ea DA.

Setšoantšo sa 2  

Palo ena e bonts'a phello ea tlhokahalo ea keketseho palong ea mechine ea khatiso ea lore e ntšitsoeng le li-pellets tse sebetsang tse jeoang ka likhoto tse nang le lipokelletso tsa DA ha li bapisoa le likhoto tse sehlopheng sa taolo ea makoloi. Aberman le Salamone, ...

Liteko tse ling li ile tsa hlahloba litlamorao tsa depbens ea DA ho li-schedule tsa tandem, moo tlhoko ea tekanyetso e hokahaneng le tlhoko ea nako ea nakoana. Sena se entsoe ka sepheo sa ho netefatsa hore liphetho tsa Aberman le Salamone (1999) 'me Salamone et al. (2001) e bonts'itse tšusumetso ea boholo ba karolelano, ho fapana le mefuta e meng e joalo ka nako. Patlisiso e sebelisang linako tse fapaneng tsa karohano ea nako (VI) / FR ka mefuta e fapaneng (mohlala, VI 30 sec / FR5, VI 60 sec / FR10, VI 120 sec / FR10) e hlahisitse mokhoa o lumellanang; ho bokella ho felloa ke matla ha DA ha hoa ka ha hatisa karabelo e akaretsang ea likhoto tse arabang ka linako tse tloaelehileng tsa VI (ke hore, tse hlokang karabelo e le 'ngoe feela kamora nako), empa li fokolitse karabelo e kholo lenaneong la VI le lekanang le tlhoko e phahameng e hoketsoeng (Correa, Carlson, Wisniecki, & Salamone, 2002; Mingote, Weber, Ishiwari, Correa, & Salamone, 2005). Liphumano tsena li tsamaellana le lipatlisiso tse bonts'ang hore ho bokella khang ea DA ha hoa ka ha senya ts'ebetso mosebetsing o tsoelang pele oa nakoana (Wakabayashi, Fields, & Nicola, 2004), le hore ho bokelloa ha depo ea DA ha ho a ka ha ama theolelo ea ho lieha (Winstanley, Theobald, Dalley, le Robbins, 2005). Ntle le moo, haloperidol ea mohanyetsi oa DA e bontšitsoe ho eketsa palo ea likarabo tse matlafalitsoeng ho likhoto tse arabelang lenaneong la DRL 72-sec (Paterson, Balci, Campbell, Olivier, & Hanania, 2010). Liphetho tsena li fana ka maikutlo a hore litlhoko tsa nakoana ha li na bothata bo boholo ho likhoto tse nang le phetoho e fetelletseng ea ho fetisoa ha DA ho li-nucleus accumbens. Ntle le matla afe kapa afe a tšebelisano ea nako kapa nako, litlhokahalo tsa tekanyo li fana ka phephetso e amanang le mosebetsi e sitisang likotlo tse ngata haholo tse nang le deplete tsa DA kapa ho hanyetsa.

Ka bokhutšoanyane, li-depositi tsa li-nucleus li bokellana ho tlosoa ha DA ho bonahala li na le litlamorao tse peli tse kholo ho karabelo ea karabelo: 1) ba fokotsa litlamorao tse ntlafatsang tseo litlhoko tsa tekanyo e lekanang li nang le tsona mabapi le ts'ebetso ea ho arabela (ke hore, karolo e nyolohang ea mosebetsi o emisitsoeng o emisitsoeng o amanang le uena. tekanyetso ea tlhoko ea tlhahiso e hlahisoang), le 2) ba ntlafatsa litlamorao tse hatellang tseo litekanyetso tse kholo li nang le tsona ho ts'ebetso e arabang (ke hore, karolo e theohelang ea ts'ebetso; ntlafatso ea khatello ea tekanyo; Salamone le Correa 2002; Salamone et al., 2001, 2007, 2009). Ntlha e 'ngoe ea bohlokoa eo u lokelang ho e nahana ha u tšohla litlamorao tsa lithethefatsi ke hore sekhahla sa motheo se hlahisitse kemiso ea matlafatso (Barrett le Bergman, 2008; Dews, 1976; McMillan le Katz, 2002). Leha sekhahla sa karabelo ea motheo e ne e se lebaka le matla la ho kenyelletsa khatello ea maemo ho Salamone et al. (2001) teko, phokotso ea sekhahla sa karabelo se bonoang ho lipampiri tse 'maloa tsa tšebetso . Hohle lipampiri tsena, ho na le kamano e pakeng tsa sekhahla sa mantlha sa karabelo tlasa maemo a taolo le boemo ba khatello bo hlahisoang ke ho bokelloa ha DA, ka ha khaello e le kholo bakeng sa linako tse hlahisang sekhahla sa karabelo (Setšoantšo sa 3). Ntle le moo, tlhahlobo ea boitšoaro ea limolek'hule e bonts'a hore lipokelletso tsa DA li hlahisa phokotseho e nyane ho tekanyo ea lehae ea ho arabela, joalo ka ha ho bonts'oa linako tsa karohano (Mingote et al., 2005; Salamone, Kurth, McCullough, Sokolowski, le Batsoala, 1993; Salamone, Aberman, Sokolowski, le Batsoala, 1999), hammoho le keketseho ea ho khefutsa (Mingote et al., 2005; Salamone, Kurth, et al., 1993;; bona hape Nicola, 2010). Mekhoa ea computational e sebelisitsoe ho tšoaea litlamorao tsa ho putlama ha DA ka sekhahla sa karabelo ho kemiso ea karolelano (mohlala, Niv, Daw, Joel, & Dayan, 2007; Phillips, Walton, & Jhou, 2007). Phillips et al. o khothalelitse hore tokollo ea DA maemong a nyutlelie e bonahala e fana ka fensetere ea menyetla ea nako eo litšenyehelo tsa litšenyehelo tsa ho fumana moputso li fokotsehileng.

Setšoantšo sa 3  

Scatterplot e bonts'a kamano lipakeng tsa motheo le litekanyetso tsa taolo ea karabelo lipakeng tsa karohano le maqhubu a karolelano ea matlafatso ha e bapisoa le boholo ba khatello ea tekanyo ea karabelo e hlahisoang ke lipokelletso tsa DA (tse hlahisitsoeng joalo ka liperesente tse kholo) ...

Boemong ba puisano ena mabapi le litlamorao tsa lithethefatsi tsa dopaminergic mabapi le ts'ebetso ea karolelano, ho bohlokoa ho hlahloba lentsoe "matlafatso ea ts'ebetso", eo ka linako tse ling e sebelisoang ho hlalosa litlamorao tsa tšebeliso ea lithethefatsi mabapi le ts'ebetso ea tekanyo. Ka kemiso e tsoelang pele ea karolelano, tlhokahalo ea keketseho e eketseha ha litekanyetso li phetheloa, 'me ho thoe "sebaka sa khefu" se hlaha sebakeng seo phoofolo e emisang ho arabela ho sona. Motho a ka hlalosa ts'ebetso ea ts'ebetso ho latela sebaka sa khefu lenaneong le tsoelang pele la litekanyetso, kapa ka ho lekanya boima ba likhoto tse arabelang litsing tse fapaneng tsa FR. Boikemisetso ba ho matlafatsa tšebeliso ea matla e ka ba sesebelisoa se sebetsang haholo sa ho khetholla liketso tsa lithethefatsi tse iketselitsoeng, le bakeng sa ho bapisa boits'oaro ba boithati ho pholletsa le lintho tse fapaneng kapa sehlopha sa lithethefatsi (mohlala, Marinelli et al. 1998; Morgan, Brebner, Lynch, & Roberts, 2002; Ward, Morgan, & Roberts, 2005; Woolverton le Rinaldi, 2002). Leha ho le joalo, ka lebaka la mathata a hlalosoang ka poleloana e boletsoeng ka holimo, ho bohlokoa ho hatisa hore polelo "matlafatso ea ts'ebetso" ha ea lokela ho sebelisoa e le sebaka sa "moputso", mme lintlha tse tsoelang pele tsa karo-karo ha lia lokela ho talingoa e le tsona tse fanang ka kotloloho ebile e le tse thata. mohato o amanang le thabo e kenelletseng e hlahisoang ke motsoako (Salamone, 2006; Salamone et al., 1997; 2009). Liphetoho tse bakoang ke lithethefatsi maemong a phomolo a tsoelo-pele a keketseho li ka bonts'a liketso liketsong tse fapaneng tsa boitšoaro le tsa methapo ea kutlo (Arnold & Roberts, 1997; Bickel et al., 2000; Hamill, Trevitt, Nowend, Carlson, & Salamone, 1999; Killeen, 1995; Ho hloka, Jones, & Roberts, 2008; Madden, Smethells, Ewan, & Hursh, 2007; Mobini, Chiang, Ho, Bradshaw, & Szabadi, 2000). Mohlala, ho fetola litlhokahalo tsa karabo ka ho eketsa bophahamo ba lenala ho fokotse lintlha tse tsoelang pele tsa khefutso (Schmelzeis le Mittleman 1996; Skjoldager, Pierre, & Mittlman, 1993). Leha bafuputsi ba bang ba tsitlallela hore sebaka sa khefu se fana ka tekanyo e tobileng ea litakatso tsa takatso ea tlhotlheletso, ho joalo ka ha ho boletsoe ke tlhahlobo ea bohlokoa ea naha Stewart (1975), ka ho hlaka haholoanyane hore na sebopuoa se tla etsa mosebetsi o mongata hakae ho fumana khothatso eo. Phoofolo e etsa khetho ea theko / melemo ea hore na e tsoelepele ho araba kapa ho se tsoelepele ho arabela, ho ipapisitse le lintlha tse amanang le matlafatso ka boeona, empa hape le holim 'a litšenyehelo tsa karabelo tse amanang le mosebetsi le litšitiso tsa nako tse behiloeng ke kemiso ea karolelano. Bakeng sa mabaka ana, litlhaloso tsa liketso tsa lithethefatsi kapa maqeba lintlheng tse tsoelang pele tsa khefutso li lokela ho etsoa ka hlokolosi, joalo ka ha ho lokela ho ba joalo bakeng sa mosebetsi o mong le o mong. Setlhare se fetolang sebaka sa khefu se ka etsa joalo ka mabaka a mangata a fapaneng. Mobini et al., (2000) a sekaseka litlamorao tsa lithethefatsi tse 'maloa ho karolelano ea karolelano ea karabo a sebelisa mekhoa e ntlafalitsoeng ke Killeen (1994), ea hlahisitseng hore ts'ebetso ea kemiso e bakoa ke tšebelisano lipakeng tsa mefuta e mengata (ts'ebetso e ikhethileng, ho kopanya le nako ea karabelo). Mobini et al. e tlaleha hore haloperidol e amme paramente ea nako ea karabo, hape e theotse paramente ea ts'ebetso, ha clozapine e eketsa paramente ea ts'ebetso. Boithuto ba morao-rao bo bonts'itse hore haloperidol ea DA ea bohanyetsi e ka hatella tekanyo e ntlafalitsoeng ea lijo e ntlafalitsoeng, le lintlha tsa khefu e tlase, leha ho le joalo e tlohela ts'ebeliso ea sesebelisoa se fumanehang ka nako e le 'ngoe empa se sa ratehe haholo (Pardo et al., 2011; Randall, Pardo, et al., 2011). Ts'ebetso tsena tsa haloperidol mosebetsing ona li ne li fapane haholo le tse hlahisoang ke lithethefatsi tse hatelang pele le takatso ea lijo (Pardo et al., 2011; Randall, Pardo, et al., 2011).

DA ANTAGONISM LE NUCLEUS ACCUMBENS DITLHAKISO TSA DAE TSE KHOLO TSA TLHALOSO E FELENG EA HO FUMANA LITLHAKISO TSA MESEBETSI EA KHETHO E FUMANENG

Joalokaha ho boletsoe kaholimo, liphoofolo li tlameha ho etsa liqeto maemong a rarahaneng a fanang ka menyetla e mengata ea ho fumana menyetla ea bohlokoa, le litsela tse 'maloa tsa ho li fumana (Aparicio, 2001, 2007; Williams, 1988). Mefuta e fetolang likhetho tsena e rarahane ebile e le mefuta e mengata, mme ha e kenye feela boleng ba matlafatso, empa le lintlha tse amanang le karabelo. Har'a lintho tsa bohlokoahali ke lintho tse kenyelletsang litšebelisano tsa theko / melemo ho latela matla le ntlafatso ea matlafatso (Hursh et al., 1988; Neill & Toka, 1981; Salamone, 2010a; Salamone le Correa 2002; Salamone, Correa, Mingote, & Weber, 2003; Salamone et al., 2005, 2007; Van den Bos, van der Harst, Jonkman, Schilders, & Spruijt, 2006; Walton, Kennerley, Bannerman, Phillips, & Rushworth, 2006). Bopaki bo bonts'ang bo bonts'a hore tekanyetso e tlase ea bahanyetsi ba DA, hammoho le tšitiso ea lehae ea methapo e bokellanang phetiso ea DA, e ama kabo e lekanang ea ho fa liphoofolo liphoofolo tse arabelang mesebetsing e lekolang ts'ebetso ea boikhethelo e thehiloeng boitekong (Floresco, St. Onge, Ghods-Sharifi, le Winstanley, 2008; Floresco, Tse, & Ghods-Sharifi, 2008b; Hauber & Sommer 2009; Salamone et al. 2003, 2005, 2007).

Mosebetsi o le mong o 'nileng oa sebelisoa ho lekola litlamorao tsa manolo a dopaminergic mabapi le karabelo ea karabelo ke ts'ebetso e fanang ka likhoto khetho ea mochini o hatellang o matlafatsoang ka ho tlisa lijo tse ratoang (mohlala, li-pellts tsa Bioserve; hangata li fumanoa lenaneong la FR 5), kapa ho atamela le ho ja lijo tse sa ratoang haholo (labop) tse fumanehang ka nako e tšoanang ka phapusing (Salamone et al., 1991). Likhoto tse koetliselitsoeng tlas'a maemo a motheo kapa a maemo a taolo li fumana boholo ba lijo tsa bona ka khatello ea lever, hape li ja boholo bo fokolang ba chow. Litekanyetso li tlase tsa litekanyetso tsa bahanyetsi ba DA, tse thibelang D1 kapa D2 li-receptor tsa malapa (cis-flupenthixol, haloperidol, raclopride, eticlopride, SCH 23390, SKF83566, ecopipam), e hlahisa phetoho e kholo ea karolelano ea likarabo ho likhoto tse etsang mosebetsi ona; li fokotsa khatello ea lever e matlafalitsoeng ke lijo empa li eketsa ho kenella ha chow (Cousins., Wei, & Salamone, 1994; Koch Schmid, & Scnhnitzler, 2000; Salamone et al., 2002; Salamone, Metsoala, Maio, Champion, Turski, & Kovach, 1996; Salamone et al., 1991; Sink et al. 2008; Worden et al. 2009).

Ts'ebeliso ea mosebetsi ona ho lekola boitšoaro bo amanang le boikitlaetso e netefalitsoe ka mekhoa e mengata. Litekanyetso tsa bahanyetsi ba DA tse hlahisang phetoho ho tloha ho phepelo ea lever ho ea ho tse ling ha li ame ho ja lijo tse felletseng kapa khetho e teng lipakeng tsa lijo tsena tse peli tse khethehileng litekong tsa khetho ea mahala (Koch et al., 2000; Salamone et al., 1991). Ho fapana le hoo, takatso ea khatello ea lijo e tsoang lihlopheng tse fapaneng, ho kenyeletsa amphetamine (Mousse et al., 1994), fenfluramine (Salamone et al., 2002) le lihanyetsi tsa cannabinoid CB1 (Sink et al., 2008) e hlotsoe ho eketsa tekanyo ea ho ja ka tekanyetso ea meriana e hatellang khatello ea lever. Ka mokhoa o ts'oanang, ho fetisa lijo pele ho nako ho fokolitse khatello ea khatello le ho ja haholo (Salamone et al., 1991). Ntle le moo, ka lipehelo tse phahameng (ho fihlela ho FR 20, kapa li-ratios tse tsoelang pele), liphoofolo tse sa phekoloang ka lithethefatsi li fetoha ho tloha phepelong ea lever ho kenella lenong (Pardo et al., 2011; Randall, Pardo, et al., 2011b; Salamone et al., 1997), ho bonts'a hore mosebetsi ona o tsotella moroalo oa mosebetsi. Liphetho tsena li bonts'a hore ho kena-kenana le phetiso ea DA ha ho fokotse feela phepelo ea lijo, empa ho na le moo ho sebetsang ho fetola kabo ea karabo lipakeng tsa mehloli e meng ea lijo e ka fumanehang ka likarabo tse fapaneng tsa lisebelisoa.

Phetoho ho tloha ho phehella ho lever ho kenella ho tsejoang ho likhoto tse etsang mosebetsi ona ho amahanngoa le depletions ea DA ho li-nucleus accumbens; Ho fokotseha ha khatello ea lever le ho eketseha ha palo ea batho ba jang hobane batsoali ba DA ba le depositi, hammoho le ente ea malapeng.1 kapa D2 bahanyetsi ba lelapa e ka ba karolo ea mantlha kapa likhetla tse tlasa maqhubu a nyutlelie (Batsoala le Salamone 1994; Batsoala, Sokolowski, & Salamone, 1993; Farrar et al., 2010; Koch et al. 2000; Hona joale, Arizzi, Carlson, & Salamone, 2001; Salamone et al., 1991; Sokolowski le Salamone, 1998). Kahoo, leha khatello ea lever e fokotsehile ka ho bokellana kapa ho putlama ha DA, likhoto tsena li bonts'a phetisetso ea boits'oaro mme e khetha tsela e ncha e eang mohloling o mong oa lijo.

Salamone et al. (1994) hape a theha mokhoa oa T-maze, oo matsoho a mabeli a khethiloeng a nang le bokhoni a lebisang ho matlafatso e fapaneng (mohlala, li-pellets tse 'ne, kapa li-zero tse' ne); Tlas'a maemo a mang, tšitiso e ka kenngoa letsohong ka matla a matla a tlatsetso ea lijo ho hlahisa phephetso e amanang le boiteko. Ha letsoho le phahameng le na le litšitiso sebakeng, 'me letsoho le senang tšitiso le na le likhokahanyo tse fokolang, ho tlosoa ha DA kapa ho hlekefetsoa ho theola khetho bakeng sa letsoho le phahameng la segalo le ho phahamisa khetho ea letsoho le tlase haholo ha le na thipa (Metsoala, Atherton, Turner, & Salamone, 1996; Denk, Walton, Jennings, Sharp, Rushworth, & Bannerman, 2005; Mott et al., 2009; Pardo et al., E romelletsoe phatlalatso; Salamone et al., 1994).

Joalo ka mosebetsi o ikhethileng o tšoanang, mosebetsi ona oa T-maze le ona o ntse o netefalitsoe ka boits'oaro le tlhahlobo (Mousse et al., 1996; Pardo et al., E romelletsoe phatlalatso; Salamone et al., 1994; van den Bos et al., 2006). Mohlala, ha ho se na tšitiso matsatsing a maholo, likhoto li khetha letsoho le phahameng la matlafatso, 'me ha ba haloperidol kapa ba bokella DAle e fetolang khetho ea bona (Salamone et al., 1994). Ha letsoho le nang le tšitiso le ne le e-na le lipentšele tse 'ne, empa letsoho le leng le ne le se na lipentšele, likhoto tse nang le depletions tsa DA li ne li ntse li khona ho khetha letsoho le phahameng la letsoalo, le hloa mekoallo,' me le jang li-pellets (Mousse et al., 1996). Phuputsong ea morao-rao ea T-maze le litoeba, ha haloperidol e theotse khetho ea letsoho le thipa, sethethefatsi sena ha se na tšusumetso ea khetho ha matsoho ka bobeli a ne a e-na le tšitiso sebakeng sa hae (Pardo et al., E romelletsoe khatiso). Kahoo, manopulations a dopaminergic ha a fetole khetho ea moputso o phahameng oa moputso oa lijo ka lebaka la letsoalo le tlase, mme ha e ame khethollo, mohopolo kapa mekhoa ea ho ithuta e amanang le thato ea letsoho. Liphetho tsa lithuto tsa T-maze ho litoeba, hammoho le liphumamiso ho tsoa ho lithuto tsa boikhethelo tsa FR5 / chow tse hlahang ka holimo li bontša hore litekanyetso tse tlase tsa bahanyetsi ba DA le li-depbens tsa DA li etsa hore liphoofolo li fallise khetho ea tsona ea karabo ho latela litlhoko tsa karabelo. ea mosebetsi, 'me u khethe mekhoa e theko e tlase ea ho fumana litlhatlhobo (bona maikutlo ka Salamone et al., 2003, 2005, 2007; Floresco, St. Onge, et al., 2008).

Mekhoa ea ho fokotsa litheko le eona e sebelisitsoe ho ithuta ka litlamorao tsa manonyeletso a dopaminergic. Floresco, Tse, et al. (2008) e bonts'itse hore haloperidol e arohantseng le liphetoho tsa boiteko ba DA le ha litlamorao tsa ho lieha ha nako li laoloa bakeng sa (bona Wade, de Wit, le Richards, 2000; le Koffarnus, Newman, Grundt, Rice, & Woods, 2011 bakeng sa puisano ea liphumano tse tsoakaneng ka har'a lingoliloeng ka litlamorao tsa bahanyetsi ba DA le ho theola litheolelo). Bardgett, Depenbrock, Downs, Points, & Green (2009) haufinyane tjena ho qaptjoa mosebetsi oa ho theola litheko tsa T-maze, eo ho eona lijo tse leng ka letsoho le phahameng la bokhoni bo ileng ba fokotseha tekong e 'ngoe le e' ngoe eo likhoto li khethileng letsoho leo. Mekhoa ea T-maze, e lumellang qeto ea sebaka sa ho iphapanya bakeng sa rat e ngoe le e ngoe). Phokotso ea matsapa e fetotsoe ke D1 SCH23390 le mohanyetsi oa lelapa2 lelapa la antagonist haloperidol; meriana ena e ile ea etsa hore monyetla oa hore likhoto li khethe letsoho le matla la ho matlafatsa / theko e tlase. Ho eketsa phetiso ea DA ka tsamaiso ea amphetamine ho thibetse litlamorao tsa SCH23390 le haloperidol, hape le litheko tse leeme ho khethang letsoho le matla la ho matlafatsa / le theko e phahameng, le lumellanang le lithuto tsa khetho tsa mosebelisi tse sebelisang litheko tsa DA tsa transporter knockdown (Cagniard, Balsame, Brunner, & Zhuang, 2006). Hammoho le liphetho tse ling, liphumano li tlalehiloe ke Bardgett et al. le Floresco, Tse, et al. ts'ehetsa tlhahiso ea hore maemong ohle a fapaneng, phetisetso ea DA e fana ka tšusumetso ea maikutlo a holimolimo mabapi le boits'oaro bo amanang le boikitlaetso.

LITLHAKISO TSA DAE LE BORAPI BA BANG BA HO FUMANA LITLHOHONOLOFATSO TSE KHOLO

Joalokaha ho hlahlojoa ka holimo, bahanyetsi ba DA le ho bokelloa ha DA ho ama tlhahiso ea tlhahiso, karabelo ea karabelo, le boits'oaro bo amanang le boiteko. Ho hlakile hore ha ho na sebaka se le seng sa boko kapa neurotransmitter e nkang karolo ea ts'ebetso ea boits'oaro ka thoko ho likarolo tse ling kapa lik'hemik'hale; ka lebaka leo ho bohlokoa ho hlahloba hore na libaka tse ling tsa boko le li-neurotransmitters li sebelisana joang le methapo ea dopaminergic. Lilemong tse 'maloa tse fetileng, li-laboratori tse' maloa li se li qalile ho tšoaea karolo eo likarolo tse ngata tsa boko (mohlala, amygdala, anterior cingrate cortex, ventral pallidum) le li-neurotransmitters (adenosine, GABA) li bapala ka boits'oaro bo amanang le boitlhopho (Denk et al., 2005; Farrar et al., 2008; Floresco & Ghods-Sharifi, 2007; Floresco, St. Onge, et al., 2008; Hauber & Sommer, 2009; Mott et al. 2009; Pardo et al., E romelletsoe phatlalatso; Schweimer le Hauber, 2006; van den Bos et al. 2006; Walton, Bannerman, Alterescu, le Rushworth, 2003; Walton, Bannerman, & Rushworth, 2002).

Nakong ea lilemo tse 'maloa tse fetileng, ho hatelletsoe haholo tšebelisanong ea DA / adenosine. Caffeine le methylxanthine tse ling, e leng lihanyetsi tsa adenosine tsa morao-rao, li sebetsa joalo ka lintho tse matlafatsang (Ferré et al., 2008; Randall, Nunez, et al., 2011). Libaka tse nang le boko bo ngata ba DA, ho kenyelletsa neostriatum le li-nucleus accumbens, li na le adenosine A e phahameng haholo.2A poleloana ea kamohelo (DeMet & Chicz-DeMet, 2002; Ferré et al., 2004; Schiffman, Jacobs, & Vanderhaeghen, 1991). Ho na le bopaki bo bongata ba tšebelisano ea mehala lipakeng tsa DA D2 le adenosine A2A receptors (Ferré, 1997; Fink et al., 1992; Fuxe et al., 2003; Hillion et al., 2002). Ts'ebetso ena e 'nile ea ithutoa khafetsa mabapi le ts'ebetso ea koloi e sa sebetseng e amanang le parkinsonism (Correa et al. 2004; Ferré, Fredholm, Morelli, Popoli, le Fuxe, 1997; Ferré et al., 2001; Hauber & Munkel, 1997; Hauber, Neuscheler, Nagel, & Muller, 2001; Ishiwari et al., 2007; Morelli le Pinna, 2002; Pinna, Wardas, Simola, & Morelli, 2005; Salamone, Betz, et al. 2008; Salamone, Ishiwari, et al., 2008; Svenningsson, Le Moine, Fisone, & Fredholm, 1999; Wardas, Konieczny, & Lorenc-Koci, 2001). Leha ho le joalo, litlaleho tse 'maloa li boetse li na le likarolo tsa adenosine A2A mosebetsi oa receptor o amanang le ho ithuta (Takahashi, Pamplona, ​​& Prediger, 2008), matšoenyeho (Correa le Font, 2008), le karabelo e sebetsang (Font et al., 2008; Mingote et al., 2008).

Lithethefatsi tse sebetsang ho adenosine A2A li-receptors li ama ka matla phello ea mochini oa karabelo le boitlhopho bo amanang le boiteko (Farrar et al., 2007, 2010; Font et al., 2008; Mingote et al., 2008; Mott et al., 2009; Pardo et al., E romelletsoe phatlalatso; Worden et al., 2009). Li-entra-accumbens tsa li-adenosine A2A agonist CGS 21680 e fokotse ho arabela ka kemiso ea VI 60-sec e nang le tlhokahalo ea FR10 e kopantsoeng, empa ha ea ka ea senya ts'ebetso ho kemiso e tloaelehileng ea VI 60-sec (Mingote et al., 2008), paterone e ts'oanang le e bonts'itsoeng pejana ka depletions tsa DA (Mingote et al., 2005). Litekong tse arabelang ka mokhoa oa khetho oa FR5 / chow o ts'oanang, liente tsa CGS 21680 ka har'a li-accumbens li fokotse khatello ea lever le ho eketsa ho ja haholo (Font et al.). Liphetho tsena li ne li khethehile sebakeng sa hau, hobane liente tsa CGS 21680 ho dorsal ea sebaka sa taolo ho li-drabens ha e na phello (Mingote et al., 2008; Font et al.).

Ho boetse ho bontšitsoe hore adenosine A2A bahanyetsi ba li-receptor ba ka khutlisa litlamorao tsa tsamaiso e laoloang ke DD2 bahanyetsi ba likhoto tse lekiloeng ho FR5 / chow ho fepa khetho e tšoanang ea khetho (Farrar et al., 2007; Nunes et al., 2010; Salamone et al., 2009; Worden et al., 2009). Ho feta moo, li-ente tsa "systemic" kapa "intra-accumbens" tsa adenosine A2A antxonist MSX-3 ba khonne ho thibela litlamorao tsa liente tsa intra-accumbens tsa D2 antagonist eticlopride ka likhoto tse arabang mosebetsi oa khetho ea FR5 / chow ka nako e tšoanang (Farrar et al., 2010). Boithuto bo sebelisang T-maze barriers process, adenosine A2A bahanyetsi ba bontšitsoe ho khutlisa litlamorao tsa DA D2 antagonism in rats (Mott et al., 2009) le litoeba (Pardo et al., e romelletsoe khatiso). Ho feta moo, adenosine A2A li-receptor knockout lithetsi li hanela litlamorao tsa haloperidol mabapi le khetho ea letsoho le phahameng la matlafatso / theko e phahameng ea T-maze (Pardo et al.).

Mokhoa oa litlamorao tse bonoang lithutong tsena o ipapisitse le hore na lithethefatsi tse ling li tsamaisoa ka mokhoa o fe. Leha adenosine A2A receptor antagonists MSX-3 le KW 6002 ka mokhoa o ts'epahalang le ho latela ka botlalo litlamorao tsa D2 bahanyetsi ba kang haloperidol le eticlopride ka likhoto tse arabang mokhoa oa khetho oa FR5 / chowFarrar et al., 2007; Nunes et al., 2010; Salamone et al., 2009; Worden et al., 2009), li hlahisa phetoho e bonolo ea litlamorao tsa D1 antagonist ecopipam (SCH 39166; Worden et al.; Nunes et al.). Ntle le moo, adenosine e khethiloeng haholo1 antagonist e ne e sa atlehe ka botlalo ho khutliseng litlamorao tsa DA D1 kapa D2 antagonism (Salamone et al., 2009; Nunes et al.). Liphetho tse ts'oanang li fumanoe ka likhoto le litoeba ho arabela mosebetsing oa khetho ea thibelo ea T-maze; ha MSX-3 e ile ea khona ho khutlisa phello ea D2 antagonist haloperidol mabapi le khetho ea letsoho le matlafatsang / le theko e phahameng, A1 DPCPX le bahanyetsi e ne e se (Mott et al., 2009; Pardo et al., E romelletsoe khatiso). Liphetho tsena li bonts'a hore ho na le khokahano e ikhethileng pakeng tsa lithethefatsi e sebetsanang le DA D2 le adenosine A2A li-subtypes tse amohelang (bona Lethathamo 1). Ho ipapisitsoe le lithuto tsa anatomical, ho bonahala eka sena se ka etsahala ka lebaka la mokhoa oa phepelo ea selefounu ea adenosine A1 Le A2A li-receptors libakeng tse mabatooa, ho kenyelletsa le li-nucleus accumbens (Ferré, 1997; Fink et al., 1992; Fuxe et al., 2003; Hillion et al., 2002; Svenningsson et al., 1999). Adenosine A.2A li-receptors ka tloaelo li kopanets'oa ho "striatal" le "drabens enkephalin" e nepahetseng lipakeng tsa "spiny neurons"2 li-receptor tsa lelapa, le li-receptor ka bobeli li kenella litseleng tse ts'oanang tsa ho saena. Kahoo, adenosine A2A bahanyetsi ba li-receptor ba ka sebetsa hantle haholo ho khutliseng liketso tsa D2 bahanyetsi ka lebaka la tšebelisano e tobileng lipakeng tsa DA D2 le adenosine A2A li-receptor tse fumanehang ho li-neuron tse tšoanang (Farrar et al., 2010; Salamone et al., 2009, 2010).

Lethathamo 1  

Bahanyetsi ba Adenosine receptor.

TLHOKOMELISO LE LITLHOKOMELISO: LITLHAKISO TSA BOPHELO LE BOTSOALLE

Ka kakaretso, ho na le tumellano e akaretsang ea hore li-nucleus li bokella DA le lits'ebetso tse amanang le boko li nka karolo mesebetsing e mengata e bohlokoa bakeng sa boits'oaro, le ha ho ntse ho bonahala lintlha tsa boitlamo boo. Moelelo o mong oa maikutlo sebakeng sena ke hore litlatsetso tsa lefats'e tse kang "moputso", "matlafatso", "ho ithuta", "susumetso" le "taolo ea makoloi" li akaretsa haholo hore li ka sebelisoa e le litlhaloso tse ntle tsa litlamorao tsa ho hlohlontela kapa bofetoheli ba DA. Tsena li kenyelletsa tšebetso tse 'maloa tse ikhethileng, tseo bongata ba tsona li ka qhelelanang ka tse ling ka litlolo tsa boko tse kang lithethefatsi kapa maqeba a sitisang ts'ebetso e ngoe ha a siea e' ngoe e hlile e le matla (Berridge le Robinson, 2003; Salamone le Correa, 2002; Salamone et al., 2007). Motheong oa bopaki bo hlahliloeng ka holimo, ho kena-kenana le phetiso ea DA ha ho senye "moputso" ka mokhoa o mong le o mong, hobane ho sitisoa ke phetisetso ea DA ho hlahisa likarolo tse itseng tsa boits'oaro ha motho a siea lintlha tsa mantlha tsa ho matlafatsa kapa ho susumetsa ka mokhoa o hlakileng (mohlala, ts'ebetso ea bonolo. likarabo tsa mohopolo; tšebeliso ea matlafatso).

Taba e 'ngoe ea bohlokoa ke boemo ba phapang lipakeng tsa mefuta e pharalletseng haholo e kang "ts'usumetso" le "ts'ebetso ea makoloi". Leha motho a ka leka ho latela dichotomy e thata lipakeng tsa ts'usumetso ea matla le mesebetsi ea makoloi e bokellanang DA, ha ho hlokahale hore ho etsa joalo. Ho phehisanoe ka hore "taolo ea makoloi" le "tšusumetso", leha e le ka mokhoa o fapaneng, e pheta haholo ho latela lintlha tse ikhethang tsa boits'oaro bo hlalositsoeng le lits'ebetso tsa boko tse amehang (Salamone, 1987, 1992, 2010b; Salamone le Correa 2002; Salamone et al., 2003, 2005, 2007). Tumellanong le mohopolo ona, ho a utloahala ho fana ka maikutlo a hore Steve o etsa mesebetsi e emelang libaka tse fetang pakeng tsa makoloi le lits'ebetso tse susumetsang (Salamone, 1987, 2010b; Salamone et al., 2007). Mesebetsi e joalo e ka kenyelletsa mefuta ea ts'ebetso ea ts'ebetso ea boits'oaro le mekhoa e amanang le boiteko e boletsoeng ka holimo. Nuklea e bokellanang DA e bohlokoa bakeng sa ho nolofalletsa liphoofolo ho etsa lintho tse kenyellelitsoeng ho kemiso (McCullough le Salamone, 1992; Robbins le Everitt, 2007; Robbins le Koob, 1980; Robbins et al., 1983; Salamone 1988; Wallace et al., 1983), le ho sebetsana le mathata a amanang le mosebetsi a hlahisitsoeng ke kemiso (Aberman & Salamone, 1999; Correa et al. 2002; Mingote et al., 2005; Salamone et al., 2002, 2003, 2005; Salamone, Correa, Mingote, Weber, & Farrar, 2006) le lithibelo matsatsong (Mousse et al., 1996; Salamone et al., 1994). Ntle le moo, tšusumetso e khothalelitsoeng ea karolo ea DA ea maiketsetso ea ts'ebetso ea ts'ebetso le boikitlaetso e amana le khopolo-taba ea hore li-nucleus bokellanang li bohlokoa bakeng sa ho nolofatsa ho arabela maemong a ts'ebetso ea ts'usumetso ea Pavlovian e nang le tšusumetso (Letsatsi, Wheeler, Roitman, & Carelli, 2006; Di Ciano, Cardinal, Cowell, Little, & Everitt, 2001; Everitt et al., 1999; Everitt le Robbins, 2005; Parkinson et al., 2002; Robbins le Everitt, 2007; Salamone et al., 2007).

Kahoo, ho sa tsotellehe hore liphoofolo tse nang le ts'oaetso ea ho senyeha ha li-DA li lula li lebisitsoe ho fumantseng thepa le tšebeliso ea matla a tšehetso ea mantlha, li-DA li bonahala li le bohlokoa haholo ho hlola mathata a amanang le mosebetsi a hlahisoang ke boits'oaro bo matla bo nang le litlhoko tse phahameng tsa karabelo. Sena se emela ts'ebetso e le 'ngoe ea accumbens DA, empa ha se eona feela. Joalokaha ho hatisitsoe lipampiring tse fetileng (mohlala, Salamone et al., 2007), ha ho na monyetla oa hore ebe li-DA li bokella ts'ebetso e le 'ngoe feela, mme bopaki bo tšehetsang khopolo ea hore DA e kenelletse ho matlafatso ea boikitlaetso kapa boits'oaro bo amanang le boikitlaetso ha e lumellane le ho nka karolo hoa ts'ebeliso ea sistimi ena thutong e matla ea ho ithuta (Baldo & Kelley, 2007; Beninger le Gerdjikov, 2004; Kelley et al., 2005; Segovia et al., 2011; Bohlale, 2004), likarolo tsa tšusumetso ea khothatso (mohlala: ho tiisa "ho hloka"; Berridge ka 2007; Berridge le Robinson, 2003; Wyvell le Berridge, 2001) kapa phetiso ea tumiso ea "Pavlovian"Everitt le Robbins, 2005).

Tekanyo e nkiloeng ho bonoeng boits'oaro, kapa paramente e hlahisoang ho tsoa tlhahlobisong e lokelang curve, e ka ba le lintlha tse ngata tse e tlatsetsang 'me, joalo ka ha ho boletsoe ka holimo, lipatlisiso tsa pharmacology hangata li ka arohanya lipakeng tsa lintlha tsena, hobane setlhare se ka ama motho ka matla. ha a siea e 'ngoe e hlile e le thata. Mohlala oa bohlokoa oa molao-motheo ona ke karolo ea nako ea khefu e tsoetseng pele, eo, joalokaha ho boletsoe ka holimo, e susumetsoang ke lintlha tse 'maloa (Pardo et al., 2011; Randall, Pardo, et al., 2011b). Nyeoe e 'ngoe moo ntlha ena e sebetsang haholo ke tekanyo ea menyako ea ho itšunya-tšunya ea maikutlo. Mehato e joalo khafetsa e talingoa e fana ka lintlha tsa "moputso" o sa lekanyetsoang oa "moputso", kapa esita le "hedonia", leha ho le joalo, li susumetsoa ke litlhoko tsa khatello ea litefiso le boemo ba motlakase ba hona joale (Fouriezos, Bielajew, & Pagotto, 1990). Boithuto ba morao-rao ba maqhubu a ho ikhatholla a intracranial a bonts'a hore ho feto-fetoha ha maikutlo a dopaminergic ha ho ame boleng ba moputso ka sethe, empa ho e-na le hoo ho fetola tloaelo ea ho lefa litšenyehelo tsa karabelo (Hernandez, Breton, Conover, & Shizgal, 2010). Papiso ea ho matlafatsa karabelo e boetse e sebelisitsoe lipatlisisong tse ling tse amanang le moruo oa boits'oaro, boleng ba matlafatso, le mesebetsi ea litsamaiso tsa DA (mohlala. Aparicio, 2007; Heyman, Monaghan, & Clody, 1987). Ho sebelisitsoe equation ho lekana liphetho tsa lithuto le li-schedule tsa VI, le paramethara tse tsoang lipapisong tse tšoanang (mohlala, Ro) li sebelisitsoe ho emela boleng ba matlafatso (mohlala, Herrnstein ka 1974; Ro e se e bitsoa sekhahla sa matlafatso ho tsoa mehloling e meng, 'me e amana ka nepo le boleng ba matlafatso ea meketjana e reriloeng). Joalokaha ho hlokometsoe ke Killeen (1995), ka matla, Ro e emetse "halofo ea bophelo bo sa feleng" bakeng sa foromo e loketseng li-curve. Leha ho le joalo, e sebelisitsoe ka tsela ena, Ro ha e khethoe ka mokhoa o ikhethileng boleng ba matlafatso ea lijo ka se. Ka mokhoa o nepahetseng, tekanyo ena e bonts'a boleng bo lekanyelitsoeng ba ts'ebetso eohle ea khatiso ea lever le ho ja lijo tse matlafatsang ha li bapisoa le boleng bo matlafatsang ba lintho tse ling tsohle tse arabeloang le likarabo tse fumanehang (Salamone et al., 1997, 2009; Williams, 1988). Ho na le mabaka a mangata a ka tlatselletsang molemong ona oa ho kopanya lintho, 'me ho ts'oaroa ha lithethefatsi kapa lesela ho ka hlahisa litlamorao ho "boleng ba matlafatso" bo bontšang liphetoho maemong a amanang le karabelo (Salamone, 1987; Salamone et al., 1997, 2009). Ntle le moo, ho bile le lipalo tse tšoanang tse tlatselitseng tlalehong ea ho kenyelletsa khetho ka ho lumella likhakanyo tsa khetho ea karabo kapa leeme (Aparicio, 2001; Baum, 1974; Williams, 1988), eo le eona e ka amehang ke lithethefatsi.

Ka lebaka la lintlha tsena, ho bohlokoa ho nahana ka hore na mantsoe a kang "boleng" a sebelisoa joang ho moruo oa boits'oaro le lipatlisiso tsa neuroeconomics. Boleng ba matlafatso a kenyelletso ea mosebetsi oa sesebelisoa (mohlala, sekhahla se hatellang le ho ja lijo) se kanna sa talingoa e le mohato o kopaneng o kenyelletsang boleng ba matlafatso ba boitlamo hape le boleng bofe kapa bofe ba litšenyehelo bo amanang le karabelo ea sesebelisoa. e hlokahala ho fumana tiiso. E shebiloe ka mokhoa ona, litlamorao tsa bahanyetsi ba DA kapa ho putlama ho boitšoaro bo amanang le boiteko bo ka hlalosoa ho latela litšenyehelo ho litefiso tsa karabelo tse amanang le karabelo e itseng ea tumellano, ho fapana le boleng bo matlafatsang ba khothatso ka boeona. Leha litlamorao tsa haloperidol ho bias li ka ba bonyane ha ho sebelisoa li-levers tse peli tse batlang li ts'oana (mohlala, Aparicio, 2007), li ka ba kholo haholo ha li bapisoa le likarabo tse fapaneng (mohlala, phepelo e tsamaisang leino, ho phahamisa nko kapa ho tsubella; lever e tobaneng le phihlello ea lijo; thibelo e nyolohang khahlanong le sebaka se nang le lijo).

Ntle le ho fana ka leseli ka likarolo tsa boits'oaro bo matla bo bonoang ka laboratoring, lipatlisiso mabapi le boits'oaro bo amanang le boikitlaetso le tsona li na le litlamorao tsa tleliniki. Tlatsetso e tšoauoa ka ho hlophisa bocha sebopeho sa boikhethelo ba motho, liphetoho tse makatsang kabo ea lisebelisoa tsa boits'oaro ho ntho e lemalloang (Heyman, 2009; Vezina et al., 2002), le ho bokellana ha tlhoko (Heyman, 2000). Ka tloaelo, ho na le tloaelo e matla ea ho etsa ts'ebetso ea matlafatso ea lithethefatsi le tšebeliso ea lithethefatsi, hangata ka litšenyehelo tsa mesebetsi e meng ea boits'oaro. Bakhoba ba tahi ba tla sebetsa ka thata ho fumana lithethefatsi tseo ba li ratang, ba hlōle litšitiso le mathata a mangata. Kahoo, ts'ebetso e matlafalitsoeng ea lithethefatsi ho batho e kenyelletsa mekhoa e mengata, ho kenyelletsa boikitlaetso. Bopaki ba morao-rao bo bonts'a hore thibelo ea DA ea tšusumetso e bakiloeng ke ho theoha ha moruo e bakile ho fokotseha hoa litekanyetso tse tsoelang pele tsa tekanyetso e tsubelletsoeng ke koae e nang le nicotine, leha taba ena e sa ka ea ama "euphoria" kapa "ho lakatsa" (Venugopalan et al., 2011).

Hape le ho amana le likarolo tsa ts'ebeliso ea lithethefatsi le bokhoba ba joala, lipatlisiso mabapi le boits'ebetso bo amanang le boikitlaetso li na le melemo ea ho utloisisa motheo oa neural oa matšoao a psychopathological a joalo ka psychomotor ea liehang, anergia, mokhathala le ho hloka thahasello, tse bonoang ho tepelletseng maikutlong hammoho le ho maemo a mang a kelello kapa a mokokotlo (Salamone et al., 2006, 2007, 2010). Matšoao ana, a ka bang le lipontšo tse mpe tsa boitšoaro (Demyttenaere, De Fruyt, & Stahl, 2005; Stahl, 2002), ha e le hantle e emela ho senyeha ha likarolo tsa boits'oaro ba seletsa, boiteko bo matla le khetho e amanang le boiteko, e ka lebisang mathateng mosebetsing, hammoho le meeli mabapi le ts'ebetso ea bophelo, tšebelisano le tikoloho le karabelo ea kalafo. Lilemong tse 'maloa tse fetileng, ho bile le thahasello e ntseng e eketseha kalafong ea ts'ebetso ea boits'oaro bakeng sa kalafo ea khatello ea maikutlo, e sebelisetsoang ho eketsa ts'ebetso ka tatellano ka ho sebelisa boikoetliso bo hlophisitsoeng ho eketsa phihlello ea mokuli ea ho matlafatsa le ho tseba lits'ebetso tse thibelang ts'ebetso (Jacobson, Martell, & Dimidjian, 2001; Weinstock, Munroe, & Miller, 2011). Ho feta moo, ho na le pharalletsano e kholo lipakeng tsa methapo ea kutlo e amehang mesebetsing e amanang le boiteko ho liphoofolo le lits'ebetso tsa boko tse kentsoeng ts'ebetsong ea psychomotor e liehang le anergia ho tepelletseng maikutlo (Salamone et al. 2006, 2007, 2009, 2010; Treadway & Zald, 2011). Kahoo, lipatlisiso tsa mantlha le tsa bongaka mabapi le mekhoa e amanang le boits'oaro, le taolo ea tsona ea neural, li ka ba le tšusumetso e kholo lipatlisisong tsa kliniki tse amanang le bokhoba, khatello ea maikutlo le mafu a mang.

lumela hore baa fokola

Liteboho: Boholo ba mosebetsi o bontšitsoeng tlhahlobisong ena o ne o tšehelitsoe ke thuso ho JDS e tsoang US NIH / NIMH (MH078023), le ho MC ho tsoa ho Fundació UJI / Bancaixa (P1.1B2010-43).

Merce Correa le Marta Pardo joale ba Area de Psicobiol., Dept. Psic., Universitat de Jaume I, Castelló, 12071, Spain.

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