LIPOTSO: Tlhahlobo e 'ngoe ea bokhoba ba ho lemalla mekhoa ea bokhoba ke litsebi tse itlhommeng pele tsa lefats'e. Hlokomela hore Nora Volkow ke hlooho ea NIDA, mme o boletse hore lithahasello tsa boits'oaro li kenyelletsa mekhoa e tšoanang ea mantlha le phetoho ea boko joalo ka bokhoba ba lithethefatsi.
HO ITHUTA KA HO Felletseng - Neuropsychopharmacology. 2010 Pherekhong; 35 (1): 217–238.
E phatlalalitsoe inthaneteng 2009 August 26. Doi: 10.1038 / npp.2009.110
inahaneloang
Bokhoba ba lithethefatsi ke bokuli bo khutlang bo sa feleng bo tšoauoeng ke (1) qobello ea ho batla le ho e sebelisa, (2) tahlehelo ea taolo ho fokotsa ho noa, le (3) ho hlaha ha maikutlo a mabe a maikutlo (mohlala, dysphoria, matšoenyeho, ho teneha) e bonts'ang lefu le susumetsang la ho hula ha tšebeliso ea lithethefatsi e thibeloa. Ho lemalla lithethefatsi ho nahanoa e le bothata bo kenyelletsang lintho tse amanang le ho se tsotelle le ho qobelloa ho fana ka methati e meraro: 'ho itlopa joala / tahi', 'ho tlohela / ho ameha hampe', le 'ho tsepamisa mohopolo / ho lebella' (takatso). Liphuputso tsa liphoofolo le tsa batho tsa ho nka litšoantšo li senotse lipotoloho tse arohaneng tse tsamaisang methati e meraro ea potoloho ea tahi le likarolo tsa bohlokoa tsa sebaka sa ventral tegmental le ventral striatum e le sebaka sa mantlha sa binge / botahoa, karolo ea bohlokoa bakeng sa amygdala e atolositsoeng nakong ea ho khaotsa / mpe e ama sethala, le karolo ea bohlokoa mohatong oa tebello / tebello bakeng sa marang-rang a ajoang ka bongata a kenyeletsang orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, le insula e amehang takatsong le cingulate gyrus, preorsalateral prefrontal, le li-cortices tse tlase tse ka tlase ho taolo e sitisang taolo. Phetoho ea bokhoba ba tahi e kenyelletsa neuroplasticity ho likarolo tsena tsohle tse ka qalang ka liphetoho tsamaisong ea mesolimbic dopamine le ho putlama ha li-neuroadaptations ho tloha ventral striatum ho ea ho dorsal striatum le orbitofrontal cortex mme qetellong ho senyeha ha preortal cortex, cingulate gyrus, le amygdala e atolositsoeng . Tlhaloso ea methapo ea methapo ea methapo ea maemo a fetohang a lefu la tahi e theha motheo oa ho batla lipatlisiso tsa molek'hule, liphatsa tsa lefutso le neuropharmacological neuroadaptations tse bohlokoa ho ts'ebetsong ea ho nts'etsapele le ho boloka bokhoba.
TLHOKOMELISO PUSELETSO
Tlhaloso:
Ho lemalla lithethefatsi ke bothata bo sa foleng bo khutlisetsang morao bo kileng ba tšoauoa ka (1) ho qobella ho batla le ho sebelisa lithethefatsi, (2) tahlehelo ea taolo ho fokotsa ts'ebetso, le (3) ho hlaha ha boemo bo bobe ba maikutlo (mohlala, dysphoria, matšoenyeho, irritability) ho bonts'a sesupo sa ho tlosoa setlamorao ha ts'ebeliso ea lithethefatsi e thibetsoe (e hlalosoa e le tšebeliso ea tlhekefetso ea litheko) Buka ea ho hlahloba le ea Statistical ea Mathata a kelello [DSM] ea American Psychiatric Association; Koob le Le Moal, 1997; Lethathamo 1). Tšebeliso e sa lekanyetsoang ea lithethefatsi tse sa sebetseng ka linako tse ling e fapana ka ho hlaka le tšebeliso e mpe ea lithethefatsi, tahlehelo ea taolo e lekanyelitsoeng ea tšebeliso ea lithethefatsi, le ho hlaha ha ts'ebetso e matla ea ho ts'oara lithethefatsi e khethollang ho lemalla. Sebopeho sa bohlokoa sa phapano lipakeng tsa ts'ebeliso ea lithethefatsi, tlhekefetso, le ho ts'epahala ho bonesitsoe ke data e bonts'ang hore batho ba baholo ba 15.6% (29 milione) ea batho ba baholo ba US ba tla tswela pele ho etsa ts'ebeliso ea lithethefatsi tse seng molaong kapa tse seng molaong ka nako e itseng maphelong a bona. , e batlang e le 2.9% (limilione tse 5.4) e tsoella ho ts'ebeliso ea lithethefatsi ho lithethefatsi tse seng molaong (Grant le Dawson, 1998; Grant et al a, 2004). Bakeng sa joala, 51% (limilione tse 120) ea batho ba fetang lilemo tsa 12 e ne e le basebelisi ba hona joale, mme ho basebelisi bana ba hajoale, 7.7% (18 milione) ba ile ba kopana le litekanyetso tsa tlhekefetso ea tlhekefetso kapa tlhekefetso ea joala. Bakeng sa nikotine, ho 2007, ba ka bang limilione tse 28.6% (70.9 limilione tse) ba Maamerika ba nang le lilemo tse 12 kapa ho feta e ne e le basebelisi ba hona joale ba khoeli (e fetileng) ba sehlahisoa sa koae, mme ho basebelisi bana ba hona joale, 24.2% (60.1 milione) e ne e le ba tsubang koae; 5.4% (13.3 milione) ea tsuba li-cigar; 3.2% (8.1 milione) e sebelisitse koae e sa tsubang; le 0.8% (2.0 milione) ea tsuba koae liphaepheng (Ts'ebeliso e Mpe ea Ts'ebeliso e Mpe ea Ts'ebeliso e Mpe ea Ts'ebeliso ea Litšebeletso tsa Bophelo ba kelello, 2008).
Leha boholo ba lipatlisiso tsa pele tsa neurobiology ea bokhoba ba lithethefatsi bo shebileng phello e matla ea lithethefatsi tsa tlhekefetso (analogous to comparing no use use drug and use use), tsepamiso hona joale e se e fetoha taolo e sa fetoheng le liphetoho tse mpe le tsa nako e telele tsa neuroadaptive. bokong bo lebisang ho oeleng hape. Morero oa lipatlisiso tsa morao-rao tsa tlhekefetso ea lithethefatsi ke ho utloisisa sebopeho sa liphatsa tsa lefutso / li-epigenetic, liselefouno le limolek'hule tse khahlang phetoho ho tloha ka linako tse ling, tšebeliso e mpe ea lithethefatsi ho lahleheloa ke taolo ea boits'oaro holim'a ho batla lithethefatsi le ho ts'oara lithethefatsi le ho boela o khutla hape. Kamora ho itšila nako e telele eo e leng lets'oao la ho lemalla.
Moralo oa ts'ebetso ea kelello o fanang ka mehloli ea matlafatso e ntle le e mpe bakeng sa ts'ebeliso ea lithethefatsi ke kutloisiso ea hore tšebeliso ea lithethefatsi e na le likarolo tsa mathata a taolo le tšusumetso e matla (Lethathamo 1). Mathata a taolo a tšusumetso a tšoaea ke mohopolo o ntseng o eketseha oa tsitsipano kapa mofere-fere pele o etsa ketso e sa tsitsang le monyaka, ho ikholisa kapa ho phomola ka nako ea ho etsa ketso eo. Mathata a taolo ea tšusumetso a amahangoa haholo le mekhoa e metle ea ho matlafatsa (Mokhatlo oa Mahlale oa Amerika, 1994). Ka lehlakoreng le leng, mathata a qobelloang a tšoauoa ka ho tšoenyeha le khatello ea maikutlo pele a etsa boitšoaro bo phehellang le pheko ho tsoa kelellong ka ho etsa boits'oaro bo hatellang. Mathata a qobelloang a amana haholo le mekhoa e mebe ea ho matlafatsa le ho iketsetsa.
Ho theola mokokotlo oa ho se tsitse le ho qobelloa ho hlahisa moketjana oa bokhoba ba litheko tse kopaneng oa mekhahlelo e meraro - ho itlopa joala kapa ho tahoa, ho itlhahisa / ho ama hampe, ho nahana / ho lebella, moo ho susumetsoa hangata ho atileng maemong a pele le ho ts'oaroa ho kopaneng le ho qobelloa ho busa maemong a latelang. Ha motho a tloha ho tsubellellang ho ea bohlonong, phetoho e ba teng ho tloha ho matlafatsong e ntle ea ho khanna boitšoaro bo susumetsoang ho isa ho matlafatsong e mpe le ho its'oara ho khanna boitšoaro bo susumetsoang (Koob, 2004; Lethathamo 1). Mehato ena e meraro e nkuoe e le ho hokahana, e ba matla le ho feta, 'me qetellong e lebise ho boemo ba bophelo bo tsejoang ka hore ke bokhoba (Koob le Le Moal, 1997; Lethathamo 2). Phetoho ho tloha tšebeliso ea lithethefatsi ka linako tse ling ho kenella bokhobeng e kenyelletsa neuroplasticity linthong tsena tsohle mme e ka qala ka tšebeliso ea lithethefatsi ea mantlha ho batho ba tlokotsing kapa batho ka bomong haholo-holo linako tsa nts'etsopele tsa kholo (mohlala, bocha; Koob et al a, 2008b). Tlhahlobo ea hajoale e shebisisa ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea joala, kamoo e fetohang le ho ikamahanya le lithethefatsi tsa tlhekefetso, le kamoo e sebelisanang ho hlahisa boemo ba bophelo bo tsejoang ka ho re ke bokhoba.
Mehloli ea Matlafatso: Ho Tsosa, Ts'ebetso ea Bohanyetsi, Salience ea Khothatso
Liphetoho tse susumetsoang ke lithethefatsi le meputso ea tlhaho ke karolo ea bohlokoa ea bokhoba ba tahi (Lethathamo 1). Mosebetsi oa pele ke Wikler (1952) e hatelletse tšebetso ea liphetoho liprofinseng tse amanang le ts'epahalo (mona e bitsoa bokhoba. Lihlooho li hlalositse liphetoho tsa ho tlohela e le 'tlala' kapa tlhoko ea mantlha le litlamorao tsa morphine maemong a kang 'ho khora' kapa ho khotsofatsa tlhoko ea mantlha (Wikler, 1952). Leha Wikler a pheha khang ea hore matlafatso a matla a bolokiloe esita le lithutong tse its'epileng haholo (mohlala, monyaka oa ente ea opioid enteid), ts'oaetso e hlahisitse mohloli o mocha oa khotsofalo, oa ts'usumetso e mpe (Lethathamo 1).
Khopolo ea tšusumetso e ne e hokahantsoe ka mokhoa o ke keng oa aroloa le maemo a hedonic, a maikutlo kapa a maikutlo phetohong ea bokhoba ba mohopolo oa mohanyetsi oa Solomone oa tšusumetso. Solomon le Corbit (1974) e hatisitsoeng ea hore linaha tsa hedonic, tse amehang, kapa tsa maikutlo, ha li se li qalisitsoe, li iphetola ka boits'oaro ke methapo e kholo ea methapo ka methapo e fokotsang matla a maikutlo a hedonic. Likarabo tse ntle tsa hedonic ts'ebelisong ea lithethefatsi li etsahala haufinyane kamora tlhahiso ea khothalletso, li hokahanya haufi-ufi le botebo, boleng, le nako ea matlafatso, 'me li bonts'a mamello le boikemelo kapa ho tlosoa hoa hedonic (ho hana). Ho fapana le hoo, likarabo tse mpe tsa hedonic li latela likarabo tse ntle tsa hedonic, lia lieha ho tloha qalong, li lieha ho haha ho fihla asymptote, li lieha ho bola le ho hola ka ho pepeseha khafetsa. Karolo ea merero ea mohanyetsi e qala pele ho ts'ebeliso ea lithethefatsi, e bonts'a liphetoho mokholeng oa moputso le khatello ea maikutlo, 'me hamorao e ba e' ngoe ea lisosa tse kholo tsa ts'usumetso ho ts'ebeliso ea lithethefatsi ka mokhoa oa khatello ea ho tlosoa.
Moqomong ona, ponahatso ea lefu la ho khaola kamora ho tlosoa hoa ts'ebetso ea lithethefatsi tse sa tsitsang, ebang ke tse mpe haholo kapa tse sa tsoakoang, ho hlalosoa ho latela likarolo tsa ts'usumetso tse joalo ka ho hlaha ha boemo ba maikutlo bo seng botle (mohlala, dysphoria, matšoenyeho, ho se ts'oanehe) ha phihlello ho moriana o thibetsoe (Koob le Le Moal, 2001), ho fapana le matšoao a ho its'epa, a atang ho ba ha nako e khuts'oane. Ho joalo, ba bang ba phehile khang ea hore nts'etsopele ea boemo bo bobe joalo bo ka hlalosang ho ts'epahalla ho lemalletseng bokhoba ba tahi (Russell, 1976; Baker et al a, 1987) le hore mmuso o joalo o mobe o kenya letsoho ho qobelloang ka mekhoa e mebe ea ho matlafatsa (Koob le Le Moal, 2005).
Conceptualization e 'ngoe ea liphetoho tse susumetsoang tse amanang le bokhoba ba tai e nkiloe mosebetsing oa pele ho ts'ebetso e matlafatsoang, tšusumetso ea maikutlo, boits'oaro ba boits'oaro, le ho ithuta ka mokhoa o fosahetseng, tseo kaofela li fuoang tlasa ts'usumetso ea tšusumetso ea ts'usumetso ea ts'usumetso ea ts'usumetso. Lithethefatsi li sebelisetsoa lits'ebetso bokong tse behiloeng ho tsamaisa liphoofolo ho susumetsa ka sesose bakeng sa ho boloka mefuta. Hypothesis ea ts'usumetso ea ts'usumetso e na le boleng bo bohlokoa ba ho ba le ts'ebeliso ea lithethefatsi hobane e fokotsa sepheo sa ho batla lithethefatsi ka litšenyehelo tsa meputso ea tlhaho. Tlhahlobo ea bongaka ea hore batho ba nang le mathata a ts'ebeliso ea lithethefatsi ba na le moelelo o sa tloaelehang oa ho batla lithethefatsi kantle ho meputso ea tlhaho e lumellanang le pono ea ts'usumetso ea matla.
Keketseho ea bokhoni ba ts'usumetso e hlahisoang ke lithethefatsi tsa psychostimulant e na le metso ea pele ho ts'ebetsong ea ho matlafatsa le maemo a ho batla lithethefatsi (Robbins, 1976; Thaba, 1970). Mona, ho batla lithethefatsi ho laoloa ke tlhahlamano ea khethollo e amanang le lithethefatsi e ka sebetsang hape e le liphatlalatso tse nang le maemo ha li hlahisoa ka lebaka la karabelo tse fanoang ke matla (Everitt et al a, 2008). Batho ba bangata ba pheha khang ea hore, ka ho ithuta ho kopantseng, boemo bo matlafatsang ba ho khothaletsa bo ikemisetsa ho shebana le litheko tse amanang le lithethefatsi, tse lebisang ho qobelloang ha khatello ea ho batla le ho sebelisa lithethefatsi (Hyman et al a, 2006; Kalivas le Volkow, 2005). Ts'ebetso e ka tlase ea meaho ea neural e kentsoeng ho boloka maemo a ts'usumetso ea ts'usumetso e ntse e phehella, e etsa hore ba lemaletseng ho hlaseloa habonolo hore ba boele ba oele ka nako e telele.
Pono e 'ngoe ea boikhohomoso bo mabapi le ts'usumetso ea boits'oaro, hangata e lekantsoe e le likarabo tse eketsehileng tsa ba tsamaeang le taolo e phetoang ea sethethefatsi. Paradigm ea boits'oaro ea boits'oaro e fane ka tšusumetso e kholo ea ho hlahloba eseng feela methapo ea methapo ea tahi empa hape le mohlala oa lefu la methapo ea pelo le ka bang teng nakong ea phetoho ho tloha ts'ebelisong ea lithethefatsi ho ea ho lithethefatsi. Mona, phetoho ea boemo bo khothatsang, e hlalosoang e le 'ho batla' e hokahantsoeng le ts'ebeliso e qobelloang, ho fapana le ho 'rata' e hokahaneng le likarabo tsa hedonic, ho nahanoa hore e tla hola butle-butle ka ho pepesehela lithethefatsi tsa tlhekefetso khafetsa (Robinson le Berridge, 1993).
Phetoho ea ho lemalla: Mekhoa ea ho Sebelisa Lithethefatsi, Mehlala ea Liphoofolo
Lithethefatsi tse fapaneng li hlahisa mekhoa e fapaneng ea neuroadaptations e nang le litlatsetso tse sa feleng tsa lithethefatsi. Mohlala, lithuto tse lemalloang ke opioid li kopana le boholo ba litekanyetso tsa DSM tsa ho lemalla, ho kenyelletsa mamello e ts'oanang le ho khaotsa (matšoao a khale a amanang le ho itšepa 'meleng) le matšoao a mangata a amanang le ho tlosoa. Mokhoa oa ho sebelisa lithethefatsi tse kenang kahare kapa tse tsubang, ho kenyelletsa ho tahoa, mamello, ho ja haholo, "dysphoria", ho hloka taolo ea mmele le matšoao a ho itlosa bolutu ka nako ea ho tsuba. Ho ameha haholo ka ho fumana li-opioid (ho lakatsa) ho hlaha hangata ho tlang pele mats'oao a ho khaotsa mme ho sa amanngoe le ho hlohlelletsa feela ho susumetsoa ke ho fumana moriana empa hape le ho susumetsa ho amanang le ho tlohela le boemo bo hlohlelletsang. Ho hlaha tloaelo eo ho eona moriana o lokelang ho fumanoa ho qoba letsoalo le tebileng le ho se thabe. Lithethefatsi tse ling tsa tlhekefetso li latela mokhoa o ts'oanang empa li ka kenyelletsa haholoanyane ho itlopa joala kapa ho tahoa (li-psychostimulants) kapa ho itlopa joala / ho tahoa le ho khaola / ho ama hampe ho amehang le methati ea ho lebella (nicotine le cannabinoids).
Boholo ba tsoelo-pele ea morao-rao ea ho utloisisa sebopeho sa bokhoba ba tahi, bo tsoa lipatlisisong tsa mefuta ea liphoofolo tsa lithethefatsi ho lithethefatsi tse joalo ka tse matlafatsang, li-opioid, joala, nikotini le Δ9-tetrahydrocannabinol (Δ9-THC). Le ha ho se na mohlala oa phoofolo o lematsang boemo ba motho ka botlalo, mehlala ea liphoofolo e lumella ho etsa lipatlisiso tsa likarolo tse itseng tsa ts'ebetso ea bokhoba ba lithethefatsi. Lintho tse joalo li ka hlalosoa ka mehlala ea mehato e fapaneng ea potoloho ea tšebeliso (bona ka holimo; Lethathamo 2).
Keketseho e tsoelang pele ea maqhubu le matla a ts'ebeliso ea lithethefatsi ke e 'ngoe ea liketsahalo tse kholo tsa boits'oaro tse khethollang kholo ea bokhoba ba tahi mme e na le bonnete ba litekanyetso tsa DSM:' Hangata ntho e nkuoa ka bongata le ka nako e telele ho feta kamoo e neng e reretsoe ' (Mokhatlo oa Mahlale oa Amerika, 1994). Mefuta e 'meli ea liphoofolo, e' ngoe e kenyelletsa lithethefatsi tse tsamaeang le liteko, 'me e' ngoe e kenyelletsa lithethefatsi tse iphelisang, e sebelisitsoe ho hlahloba litlamorao tsa taolo ea lithethefatsi khafetsa ho neuroplasticity methapong ea methapo e boletsoeng ka holimo. Boitšoaro ba boits'oaro hangata bo ne bo kenyelletsa taolo e pheta-phetoang ke motho ea sebelisang lithethefatsi, hangata e le psychostimulant, maemong a ikhethileng a tikoloho mme mohato o itšetlehileng hangata e ne e le ts'ebetso ea locomotor. Mona, liphoofolo tse amohetseng lithethefatsi li bonts'a keketseho e makatsang ea ts'ebetso ea locomotor ho lethal dose ea phephetso ea lithethefatsi (sensitization) ho feta taolo e neng e fumane mehato e pheta-phetoang ea liente tsa koloi.
Moralo, mohlomong o nang le bonnete bo eketsehileng ba sefahleho ba ho latela tšebeliso ea lithethefatsi ho ea bokhobeng ba lithethefatsi, o ka fumanoa mefuteng ea liphoofolo ea phihlello ea nako e telele ea boitaolo ba lithethefatsi. Mona, ho sebelisa ts'ebetso ea lithethefatsi ho kenella kahare, ho fihlella lithethefatsi ho amana le ho nyoloha ha nako ea matsatsi a mangata (Koob, 2009a). Ts'ebetso e joalo e eketsehang ea boitaolo e boetse e hlokometsoe le joala boo likhoto li noang haholo nakong ea litheko tse matla haholo le tse tloheletsoeng ho iphumanela ts'ebeliso ea mali ka ho sebelisa lijo tse sa foleng tsa metsi kapa ho pepeseha ha mouoane o sa foleng.Gilpin le Koob, 2008). Liphoofolo tse entsoeng tse itšetlehileng ka joala ka ts'epahalo li fumana maemo a joala a mali ho 100-150
mg%%, e lekanang le maemo a hlekefelitsoeng ke ba sebelisang joala bo bongata tekano. Liphetoho ho matlafatso le litlamorao tsa ts'ebeliso ea lithethefatsi li hlokometsoe kamora ho fihlella le ho eketsoa ha ts'ehetso le ho kenyelletsa ho arabela ka tekanyo e tsoelang-pele (Koob, 2009a), ho khutlisetsoa ho tlisoang ke lithethefatsi kamora ho felisoa, ho fokotsehile nako ea sepheo mohlaleng oa moputso oa moputso oa lithethefatsi (Deroche-Gamonet et al a, 2004), le khanyetso e matla ea kotlo eo ho eona phoofolo e tla fana ka kotlo e phahameng ho feta tekano ho fumana lithethefatsi (Vanderschuren le Everitt, 2004). Hore na ho nka lithethefatsi tse ntlafalitsoeng ka phihlello e atolositsoeng ho bonts'a maikutlo a moputso (kapa oa tšusumetso) kapa mmuso o haelloang ke moputso, kapa bobeli ba tsona, li lula li ntse li tsoela pele lipuisanong (Vezina, 2004).
NEUROCIRCUITRY OF ADDICTION: Bopaki ba NEUROPSYCHOPHARMACOLOGICAL TOBELA Thutong ea BOPHELO
Binge / Mofuta oa Intoxication
Kutloisiso ea rona ea methapo ea methapo ea kutlo e mabapi le litlamorao tse matlafatsang tsa tlhekefetso e ka ts'oaroa ho fihlela ts'ebetso ea ho tsebahatsa tsamaiso ea moputso bokong ka ho sibolloa ha moputso oa ts'ebetso ea ts'ebetso ea motlakase ka ts'ebetso ea ts'usumetso ea motlakase ka Olds and Milner (1954). Moputso oa ho hlohlelletsa Brain ho kenyelletsa li-neurocircuitry tse atileng bokong, empa libaka tse tebileng ka ho fetisisa tse hlalositsoeng ke litheko tse tlase haholo li kenyelletsa sehlopha sa methapo ea methapo ea methapo e hokahanyang sebaka sa "ventral tegmental tegmental" (VTA) ho "basral forebrain"Ba baholo le Milner, 1954). Lithethefatsi tsohle tsa tlhekefetso, ha li fanoa ka mokhoa o hlakileng, li fokotsa meputso ea mehopolo ea boko (ke hore, moputso o eketsehileng; Kornetsky le Esposito, 1979) mme ha o fanoa ka mokhoa o sa lekanyetsoang ho eketsa meputso nakong ea ho ntshwa (ke hore, moputso o fokotsehileng; bona ka tlase). Le ha pele ho ne ho tsepamisoa maikutlo haholo holim'a karolo ea mananeo a monoamine a ntseng a nyoloha mokokotlong oa medial forebrain ka moputso, norepinephrine ea pele (Stein, 1962) ebe dopamine (Crow, 1973; Bohlale, 1978), lits'ebetso tse ling tsa nondopaminergic tse bokaholimo ba medial forebrain li na le karolo ea bohlokoa ho phetheng moputso oa ts'ebetso ea boko (Hernandez et al a, 2006). Ho joalo, mosebetsi o mong o fana ka maikutlo a hore ts'ebetso ea ts'ebetso ea "midbrain dopamine" e na le likarolo tse ngata ho fana ka ts'usumetso ea ho hlohlelletsa tikoloho (Robinson le Berridge, 1993) ho holisa ts'ebetso ea boits'oaro bo lebisitsoeng ho sepheo (Salamone et al a, 2007) kapa ts'ebetso ka kakaretso (Le Moal le Simon, 1991). Haufinyane tjena, khopolo-taba e hlahisitsoe ea hore nako ea dopamine ea ho saena ke ntho ea bohlokoa, ka nako e potlakileng ea ho etsa moputso le boleng ba liphetho tse boletsoeng esale pele tsa boits'oaro le ts'ebetso e tsitsitseng ea tokollo ea dopamine e nkile karolo ea khethollo ho ho fana ka phello e nolofalletsang litsamaiso tse itseng tse amanang le boits'oaro (Schultz, 2007). Sebetsa sebakeng sa litlamorao tse matlafatsang tsa lithethefatsi tsa tlhekefetso li ts'ehetsa hypothesis ena moo mesolimbic dopamine system e bohlokoa bakeng sa litlamorao tse matla tsa lithethefatsi tsa psychostimulant empa o na le ts'ebetso e nolofalletsang bakeng sa lithethefatsi tsohle tsa tlhekefetso.
Melemo e matla ea meputso ea lithethefatsi tsa psychostimulant ke khale e tsejoa ho itšetleha ka ts'ebetso ea mesolimbic dopamine system, empa ts'ebetso ea ts'ebetso ena ha e bohlokoa bakeng sa litlamorao tse matla tsa litlhare tse ling tsa tlhekefetso (Koob, 1992; Nestler, 2005; Hnasko et al a, 2005). Liso tsa tsamaiso ea methapo ea tsebe ea mesocorticolimbic duramine e fana ka matla a emisang matla a matlafatsang a cocaine le -amphetamine (McGregor le Roberts, 1993). Ka lehlakoreng le leng, liso tsa dopamine ka ho khetheha ka li-dopamine bokong ba nyutlelie le 6-hydroxydopamine li ile tsa sitoa ho thibela heroin kapa boits'elo ba ethanol, bo tšehetsang hypothesis ena (Koob le Le Moal, 2006).
Ho sebelisa mokhoa oa ho itaola kahare (Lethathamo 1) le maemo a makatsang a sebaka (Lethathamo 1), li-opioid le joala li bontšitsoe hore li itlhomme ka kotlolloho VTA. Li-opioids li boetse li etsa tlhahiso ea maemo a sebaka ha li kenngoa ka har'a VTA. Li-opioids, phencyclidine, le psychostimulants li itlhahela ka kotlolloho ka har'a li-nucleus tsa li-nucleus, mme li-psychostimulants li hlahisa sebaka se ikhethileng sa sebaka ha se kenngoe ka har'a li-nucleus accumbens. Cocaine le phencyclidine ka boeona e ipehile ka kotloloho cortex e ka pele (McBride et al a, 1999). Sistamine ea mesolimbic dopamine e hlahisoa ke tsamaiso e matla ea li-opioid, ethanol, nikotine, le Δ9-THC (Di Chiara le Imperato, 1988).
Intravenous nicotine self-management e thibetsoe ke marapo a amanang le neurotoxin ka ho khetheha a mesocorticolimbic dopamine system, mme ketso ea neuropharmacological e kentsoe tšebetsong ea ts'ebetso ea ho lokolla dopamine ka kotloloho ho VTA le hape ka mokhoa o ikhethileng ka har'a li-nucleus accumbens (Watkins et al a, 2000). Leha ho le joalo, moputso oa nicotine o lekantsoeng ke khetho ea sebaka se ikhethileng o bonahala o ikemetse ka mokhoa o ikemetseng oa mesocorticolimbic dopamine system (Laviolette et al a, 2002). Likarolo tse ling tse hlahisoang ke moputso oa nicotine li kenyelletsa mats'oenyeho a cholinergic ho "penunculopontine nucleus"Yeomans le Baptista, 1997). Ho VTA, ts'ebetso ea βSubunit ea 2 ea li-nicotinic receptors e bonahala e le bohlokoa bakeng sa ts'ebetso ea nicotine ea dopamine neurons (Mameli-Engvall et al a, 2006). Lithuto tsa Neuropharmacological ho cannabinoids li amme mekhoa ea cannabinoid le opioid ka bobeli. Opioid le cannabinoid CB1 antagonists block inravenous self-management of Δ9-THC ho litšoene tsa squirrel (Justinova et al a, 2003). E ts'oanang le lithethefatsi tse ling tsa tlhekefetso, Δ9Tsamaiso ea -THC e kenya ts'ebetsong ho lokolloa ha dopamine ka khubung ea li-nucleus accumbens (Tanda et al a, 1997).
Ka hona, lithethefatsi tsohle tsa tlhekefetso li kenya tšebetsong mesolimbic dopamine system, empa bopaki bo bongata bo fana ka maikutlo a hore ho matlafatsoa ha ts'ebetso ea dopamine ho etsahala maemong a li-nucleus, o fana ka maikutlo a ho kenya letsoho ha ts'ebetso ea potoloho ea bohlokoa ea ho matlafatsa libakeng tsena tsa boko (Koob, 1992; Nestler, 2005).
Ntho e bohareng ea amygdala (CeA) le eona e na le mosebetsi oa bohlokoa liketsong tse matlafatsang tsa lithethefatsi tsa tlhekefetso. Microinjections ea dopamine D1 bahanyetsi ba "receptor antagonists" ho tsa tsamaiso ea koae ea koae (CeA block cocaine)Caine et al a, 1995; McGregor le Roberts, 1993). Sebaka se hlokolosi haholo bakeng sa γ-aminobutyric acid (GABA) le mohanyetsi oa opioid oa taolo ea joala ka molomo ho likhoto tse sa ts'ehetsoeng e ne e le CeA (Hyytia le Koob, 1995; Heyser et al a, 1999). Metsoako ea CeA e thibela taolo ea joala ka molomo (Moller et al a, 1997). Bahanyetsi ba Serotonin-3 ba kentsoeng ts'ebetsong ea ts'ebetso ea molomo ea CeA block ho litoeba tse sa ts'epahaleng, phello e nahanoang hore e ka kenyelletsa bokhoni ba bahanyetsi ba serotonin-3 receptor antagonists ho thibela ho lokolloa ha lithethefatsi tsa dopamine (Dyr le Kostowski, 1995).
Sesebelisoa se ka sehloohong se tsoang ka har'a li-nucleus accumbens ke ho ventral pallidum / substantia innominata. E tsamaellana le li-nucleus tse bokellanang e le karoloana ea bohlokoa bakeng sa moputso oa lithethefatsi, lesapo la pallidum ea ventral le sebetsa hantle haholo ho thibela tšusumetso ea ho sebetsa bakeng sa koae e kenang kahare le lera la heroine (Hubner le Koob, 1990; Robledo le Koob, 1993). Ntle le moo, blockade ea dopamine le GABAA li-receptors ka hare ho pallidum ea "ventralum" li thibela litlamorao tse matlafatsang tsa joala (Melendez et al a, 2004; June et al a, 2003). Kahoo, likarolo tsa "ventral pallidum" ha li na ho ba bohlokoa feela bakeng sa ts'ebetso e tsoelang pele ea lets'oao la moputso oa lithethefatsi empa hape e ka fetoloa ka kotloloho ke lithethefatsi tsa tlhekefetso.
Dorsal striatum ha e bonahale e na le karolo e kholo litlamorao tse matla tsa tlhekefetso ea lithethefatsi empa e bonahala e hloaa nakong ea nts'etsopele ea ho batla lithethefatsi tse tlamang (Everitt et al a, 2008). LNUMX-Hydroxydopamine lesions ea dorsal striatum ha e thibele mosebetsi oa locomotor oa koae kapa ho itaola ka mokhoa oa cocaine (Roberts, 1992) empa thibela libopeho tse susumetsang tse bakoang ke li-amphetamine (Kelly le Iversen, 1976; Creese le Iversen, 1974). Ho sebelisa kemiso ea tatellano ea bobeli (Lethathamo 1), lesions ea li-nucleus accumbens le basolateral amygdala li thibetse ho fumanoa ha k'hok'heine (Whitelaw et al a, 1996). Ka mokhoa o ts'oanang, ha methapo e bokellanang mantlha e ne e hloaetsoa ka lehlakoreng le leng la boko 'me e kopantsoe le dopamine receptor blockade kontinenteng ea dorsal striatum, ha ho na phello e ileng ea bonoa liphoofolong hanghang kamora ho hapa, empa ho fokotseha haholo ha ho batloa ke koae ho ile ha bonoa ho litoeba tse nang le setala. ho araba lenaneong la odara ea bobeli (Belin le Everitt, 2008). Liphetho tsena li bonts'a hore dorsal striatum e kanna ea ba le karolo e nyane ho litlamorao tse matla tsa lithethefatsi tsa psychostimulant empa e le karolo ea bohlokoa phetolelong ea ts'ebeliso e qobelloang (Everitt et al a, 2008).
Tlhahiso-leseling e nang le litoeba tsa "knockout" e boetse e fana ka leseli la bohlokoa ho karolo ea dopamine liphellong tse ntle tsa lithethefatsi tsa tlhekefetso. Ka litoeba tse fetotsoeng ka liphatsa tsa lefutso le ho haella ha dopamine D1 receptor u se ke ua iketsetsa k'hok'heine (Caine et al a, 2007). Leha tlaleho ea pele ea hore litoeba tsa "dopamine transporter" (DAT) Knoutout li ile tsa tsoela pele ho iphelisa ka koae (Rocha et al a, 1998) a belaella ts'ebetso ea DAT liphellong tse matlafatsang tsa cocaine, phuputso ea morao-rao e bonts'itse hore liphoofolo tse fetotsoeng tse hlahisitseng DAT tse sa tlamang k'hok'heine empa e neng e sebetsa joalo ka sesebelisoa sa dopamine reuptake ha e bonts'a moputso oa cocaine o lekantsoeng ke sebaka se khethiloeng sa sebaka (Chen et al a, 2006a). Liphetho tsena li tšehetsa khopolo-taba ea karolo ea bohlokoa ea DAT liphellong tse matlafatsang tsa cocaine.
Motheong oa motsoako ona, ho hlahisitsoe potoloho ea pele ea neurobiological bakeng sa moputso oa lithethefatsi (Koob, 1992) e ntlafalitsoeng le ho holisoa (Koob le Nestler, 1997; Setšoantšo sa 1). Sebaka sa ho qala potoloho ea moputso e ne e le setlatsetso sa 'mele oa morara, se neng se entsoe ka likhoele tse ikopantseng tse kopanyang ka bokhabane ba lefutso le li-nucleus tse kopaneng le hypothalamus le VTA (Nauta le Haymaker, 1969) le ho kenyelletsa litsela tse nyolohang tsa monoamine tse kang sisteme ea mesocorticolimbic dopamine.
Ketso ea pele ea moputso oa lithethefatsi e ne e le hypothesised ho itšetleha ka ho lokolloa ha dopamine ka har'a li-bokellase tsa nucleus bakeng sa koae, amphetamine, le nikotine; ts'ebetso ea opioid peptide activation ho VTA (dopamine activation) le nucleus accumbens (e ikemetseng ea ts'ebetso ea dopamine) bakeng sa opiates; le GABAA Sistimi e bokellaneng ea li-nucleus e bokellana le li-amygdala bakeng sa joala. Li-nucleus accumbens li fumaneha ka mokhoa o loketseng ho fumana tlhaiso-leseling ea bohlokoa ho tsoa ho amygdala, frontort cortex, le hippocampus e ka fetoloang molemong oa ts'ebetso ka ho hokahanya le tsamaiso ea makoloi ea extrapyramidal. Kahoo, karolo ea pele ea bohlokoa ea li-nucleus bokella e thehiloe bakeng sa litlamorao tse matlafatsang tsa lithethefatsi, ka karolo e tšehetsang CeA le ventral pallidum (Litšoantšo 1 'me and2a2a).
Withdawal / Boemo bo Fosahetseng ba Boemo
Mokhatlo oa neuroanatomical o ile oa bitsa amygdala e atolositsoeng (Heimer le Alheid, 1991) e ka emela kemiso e tloaelehileng ea anatomical e kopanyang lits'ebetso tsa khatello ea kelello le lits'ebetso tsa ts'ebetso ea hedonic ho hlahisa maemo a mabe a maikutlo a khothalletsang mekhoa e mebe ea ho matlafatsa e amanang le nts'etsopele ea temallo. Amygdala e atolositsoeng e entsoe ka CeA, bethe ea "stria terminalis" (BNST), le sebaka sa phetoho ho subregion ea medial (khetla) subregion ea nucleus accumbens (Setšoantšo sa 2b). E 'ngoe le e' ngoe ea libaka tsena e na le lintho tse tšoanang tse tšoanang le tsa potoloho ea lefatše.Heimer le Alheid, 1991). Amygdala e atolositsoeng e amohela liphatlalatso tse ngata tse tsoang liphoofolong tse kang litho tsa basolatal amygdala le hippocampus 'me e romella thepa e kenang karolong ea moea ea pallidum le sepheo se seholo ho hypothalamus ea morao-rao, ka hona, e ntse e hlalosa libaka tse ling tsa bokong tse amanang le li-classical limbic (maikutlo) dibopeho tse nang le tlhahiso ya motor extrapyramidal motor system (Alheid et al a, 1995). Amygdala e atolositsoeng haesale e tšelisoa hore e be le karolo ea bohlokoa eseng feela maemong a tšabo (Le Doux, 2000) empa hape le karolong ea maikutlo ea ts'ebetsong ea bohloko (Neugebauer et al a, 2004).
Ka har'a system neuroadaptations ea ho pepesetsoa lithethefatsi ka nako e telele e kenyelletsa ho fokotseha ha ts'ebetso ea li-neurotransmitter system ho li-neurocircuits tse kentsoeng litlamorao tse matla tsa lithethefatsi tsa tlhekefetso. Khopolo-taba e 'ngoe e tummeng ke hore ts'ebetso ea dopamine e sekisetsoa maemong a bohlokoa a potoloho ea bokhoba ba tahi, joalo ka ho khaotsa,' me e lebisa ho khothatsong e amanang le tšusumetso e amanang le lithethefatsi le kutloisiso e eketsehang ea lithethefatsi tse hlekefelitsoeng (Melis et al a, 2005; bona lithuto tsa kelello tsa kelello ka tlase). Ho tlosoa ha Psychostimulant ho batho ho amana le mokhathala, ho fokotseha ha maikutlo le ho khutlisetsoa hoa psychomotor, 'me ho liphoofolo ho amana le tšusumetso e fokotsehileng ea ho sebeletsa meputso ea tlhaho (Barr le Phillips, 1999) le mesebetsi e fokotsehileng e fokotsehileng (Pulvirenti le Koob, 1993), litlamorao tsa boits'oaro bo ka kenyelletsang tšebetso ea dopaminergic e fokotsehile. Liphoofolo nakong ea phumollo ea amphetamine li fokotsehile ho arabela ka kemiso e tsoelang pele ea tekanyo ea tharollo e monate, 'me karabelo ena e fokotsehileng e ile ea khutlisoa ke dopamine karolo ea agonist terguride (Orsini et al a, 2001), ho fana ka maikutlo a hore molumo o tlase oa dopamine o kenya letsoho ho fokolng ha sepheo se amanang le ho tlosoa ha psychostimulant. Ho theoha ha ts'ebetso ea sisteme ea mesolimbic dopamine le ho fokotseha ha serotonergic neurotransmission ho li-nucleus tsa bokellane ho etsahala nakong ea ha ho tlosoa lithethefatsi ho tloha lithethefatsing tsohle tse kholo tsa tlhekefetso lithutong tsa liphoofolo (Rossetti et al a, 1992; Weiss et al a, 1992, 1996).
Karolo ea bobeli ea sethala sa ho tlohela / ho se sebetse hantle ke mokhoa o pakeng tsa tsamaiso ea methapo e fapaneng e amanang le khatello ea methapo le eona e ka sebetsanoang le khatello ea methapo ea khatello ea kelello le lits'oaetso tse khelohang boitekong ba ho hlola boteng bo sa feleng ba pherekano. lithethefatsi ho khutlisetsa ts'ebetso e tloaelehileng le ha ho na le lithethefatsi. Ka bobeli hypothalamic-pituitary-adrenal axis le khatello ea kelello / tsamaiso e arolelanoang ke corticotropin-releasing factor (CRF) e hlahisoa nakong ea ho khaotsa ho tsoa taolong e sa lekanyetsoang ea lithethefatsi tsohle tse kholo tse nang le monyetla oa tlhekefetso, ka karabelo e tloaelehileng ea adrenocorticotropic hormone, corticosterone, le amygdala CRF nakong ea ho ikhula ho matla (Koob, 2008; Koob le Kreek, 2007). Ho khaohana le lithethefatsi tsohle tsa tlhekefetso ho boetse ho etsa hore ho be le se sa tsikinyeheng kapa ho tšoenyeha, moo CRF le lits'ebetso tse ling tse amanang le khatello ea maikutlo (ho kenyeletsoa le litsela tsa Noradrenergic) li nang le likarolo tsa bohlokoa.
Litlamorao tse susumetsang tsa ho khaotsa ho sebelisa lithethefatsi li ka lekanngoa ka ho sebelisa mokhoa oa ho itlosa bolutu (Hand et al a, 1988), le lethalinyana la opioid karolo ea agonist luprenorphine ka mokhoa o hlakileng le lona le fokotse mokhoa oa ho tsofala o hlahisoang ke ho tlosoa hoa opioid o tsoang pele. Tsamaiso ea tsamaiso ea CRF1 receptor antagonist le tsamaiso e etsoang ka kotloloho ea intracerebral ea CRF ea peptide1/ CRF2 antagonist e boetse e fokotse mekhoa e khothalletsang sebaka ea ho khaotsa ho ikhula (opioid)Stinus et al a, 2005; Heinrichs et al a, 1995). Barekisi ba sebetsang ba Noradrenergic ba laoloang ka kotloloho ho BNST e koetsoeng ho koenya sebaka, ba fana ka bohlokoa ba ho tsosa moferefere karabisong ea khatello ea maikutlo e latelang ho tlosoa ha lithethefatsi ho hobe (Delfs et al a, 2000). Ka sebele, meriana ea khale e sebelisetsoang ho phekola ho tlosoa hoa mmele ho batho ba hlekefetsang ba heroin le lino tse tahang e kenyeletsa α-drenergic lithethefatsi (mohlala, clonidine) tse thibelang ho hlaha ha noradrenergic le ho fokotsa mats'oao a ho itlopa joala le ho khaotsa ha heroin.
Motho e mong ea khethang mathata a tlisoang ke ho khaotsa ho sebelisa lithethefatsi ke dynorphin. Bopaki bo bongata bo bonts'a hore dynorphin e eketseha ka har'a li-nucleus accumbens ka lebaka la ts'ebetso ea dopaminergic, hape, hore ts'ebetso e mengata ea dynorphin e ka fokotsa ts'ebetso ea dopaminergic. κ-Opioid agonists e tebile, 'me ho khaotsa koae, opioid le ethanol ho amahanngoa le dynorphin e ntseng e eketseha ka har'a li-nucleus accumbens le / kapa amygdala (Koob, 2008). Mokhelo ke salvidorin A, e leng a κ-agonist e hlekefetsoa ke batho, empa sena se ka bonts'a litlamorao tsa eona tse hallucinogenic ho fapana le thepa efe kapa efe e khahlisang (Gonzalez et al a, 2006).
Karabo e 'ngoe e tloaelehileng e lipakeng tsa tsamaiso ea ho khaotsa ho matla le ho ithiba ho tloha ho litlhare tsohle tse kholo tsa tlhekefetso ke ponahatso ea likarabo tse joalo ka letsoalo. Mohlala, ho ikhula taolong e khafetsa ea koae ho hlahisa karabelo e kang ea ho tšoenyeha ka tekanyo e phahameng le tekanyo ea ho patela, tseo ka bobeli li khutlisoang ke bahanyetsi ba CRF. Ka mokhoa o ts'oanang, ho tlosoa hoa ethanol ho hlahisa boits'oaro bo ts'oenyehileng bo khutlisoang ke tsamaiso ea intracerebroventricular ea CRF1/ CRF2 bahanyetsi ba peptidergic, tsamaiso ea tsamaiso ea CRF e nyane ea molek'hule1 antagonist, le microinjection ea peptidergic CRF1/ CRF2 antagonist ho amygdala (Funk et al a, 2006; Koob, 2008). Barekisi ba CRF ba kentse li-intracerebroventricularly kapa ka mokhoa o hlophisitsoeng ba boetse ba thibela likarabo tse ka 'nang tsa tšoenyeha joalo ka bahatelli ba hlokometsoeng nakong ea ha ba sa itšireletsa khafetsa ethanol e sa feleng, le litlamorao tsa bahanyetsi ba CRF ba fumanehile sebakeng sa CeA (Koob, 2008). Ho khaotsa ho noka ho tloha ho nicotine ho hlahisa likarabo tse kang tsa ho tšoenyeha tse khutliselitsoeng ke bahanyetsi ba CRF (Tucci et al a, 2003; George et al a, 2007).
Ka hona, ho tlosa ka sekhahla ho amana le liphetoho tse ka hare ho sistimi e bonts'ang ho fokotseha hoa ts'ebetso ea dopaminergic tsamaisong ea mesolimbic dopamine le pakeng tsa tsamaiso ea methapo ea li-neurotransmitter tse fanang ka khatello ea maikutlo le litlamorao tse joalo ka CRF le dynorphin. Lits'ebetso tse ling tsa neurotransmitter tse tsejoang ho ameha ho hoebetheng ha maikutlo ho litlamorao tsa tšusumetso ea lithethefatsi ho kenyelletsa norepinephrine, ntho P, vasopressin, neuropeptide Y (NPY), endocannabinoids, le nociceptin (Koob, 2008).
Preoccupation / Ketso ya ho lebella (ho lakatsa) Mothati
Boiketsetso / ho lebella kapa ho lakatsa moketjana oa ts'ebeliso ea lithethefatsi haesale ho nahanoa hore ke ntho ea bohlokoa ea ho khutlela ho batho hape ho hlalosa tlhekefetso e le bothata bo sa foleng ba ho khutla hape. Leha e kopantsoe hangata le kaho ea ho lakatsa, ho labalabela ka bobeli Ho bile thata ho lekanya ka kliniki (Tiffany et al a, 2000) mme khafetsa ha e tsamaellane hantle le ho khutla hape. Leha ho le joalo, sethala sa ts'ebetso ea lithethefatsi tseo ho tsona motho a khutlisetsang ts'ebeliso ea lithethefatsi kamora ho khaotsa ho lula e ntse e le phephetso ho tsebiso ea methapo ea methapo le methapo ea meriana bakeng sa kalafo. Mefuta ea liphoofolo ea ho lakatsa e ka aroloa ka likarolo tse peli: ho batla lithethefatsi ho susumetsoa ke lithethefatsi kapa ho susumetsoa ke tšebeliso ea lithethefatsi, le ho batla lithethefatsi ho susumetsoa ke khatello ea maikutlo kapa boemo bo seng botle ba maikutlo, hangata e le boemo ba khatello ea maikutlo, bo thibeloang nako e telele (sheba Phetoho ea ho lemalla: mekhoa ea ho sebelisa lithethefatsi, karolo ea mehlala ea liphoofolo).
Bopaki bo bongata bo tsoang liphuputsong tsa liphoofolo bo fana ka maikutlo a hore ho khutlisetsoa ka lithethefatsi ho kenelletse sebakeng sa medial prefrontal cortex / nucleus accumbens / ventral pallidum potoloho e haptjoang ke neurotransmitter glutamate (McFarland le Kalivas, 2001). Ka lehlakoreng le leng, ho khutlisetsoa kahare ho cue ho kenyelletsa ho kenyelletsa basyati ea basolateral e le karoloana ea bohlokoa e nang le ts'ebetso ea phepo ea pele ea phepo ka ts'ebetso ea pele ho cortex e kenyelletsang ho khutlisetsong e tlisitsoeng ke lithethefatsi (Everitt le Wolf, 2002; Weiss et al a, 2001). Momahano ea tšusumetso ea pele e neng e entsoe ka sepheo sa ho tlosa sepheo sa opioid (se nang le boemo bo tlisoang) e boetse e itšetleha haholo ka basolateral amygdala (Schulteis et al a, 2000), hape lintho tse susumetsang li ka ba le bohlokoa bo susumetsang (Kenny et al a, 2006). Liphetoho tsa Neurocircuitry tse amanang le ho khutlisetsoa ha lithethefatsi le lithethefatsi ka mor'a ho felisoa li hokahantsoe le tsela ea glutamatergic ho tloha pele ho cortex ho ea bokong ba li-nucleus accumbens, porojeke ea dopamine e tlohang ho VTA ho ea methapo ea methapo ea methapo pele ho nako. ho ventral pallidum (Kalivas le O'Brien, 2008).
Ho fapana le moo, ho khutlisetsoa ka matla kelellong ea karabelo e amanang le lithethefatsi mefuteng ea liphoofolo ho bonahala ho ipapisitse le ts'ebetso ea CRF le norepinephrine likarolo tsa amygdala tse atolositsoeng (bobeli ba CeA le BNST; bakeng sa litlhahlobo, bona Shaham et al a, 2003; Shalev et al a, 2002). Ho thibela pelehi, ho hlalosoang haholo mefuteng ea ho ts'epa joala, ho bonahala ho kenyelletsa ho feteletseng ha glutamatergic le lits'ebetso tsa CRF, hangata ho amygdala e atolositsoeng, leha ho le joalo ka tekanyo e kholo sena se ntse se lokela ho hlahlojoa.de Witte et al a, 2005; Valdez et al a, 2002).
Lithuto tsa batho tse lemalloang ke koae li bonts'a ts'ebetso e sa sebetseng mesebetsing e kenyang tlhokomelo, ho tenyetseha ha kelello, le ho lieha ha moputso tse khutliselitsoeng pakeng tsa methapo ea maikutlo le ea orbital, hammoho le tšenyo ea sebaka, ea mantsoe le ea memori e hlokomolohang e kopantsoeng ke hippocampus, le mefokolo ena e ka bolela sephetho se sebe sa kalafo (Aharonovich et al a, 2006; Bolla et al a, 2003). Lithuto tsa liphoofolo tse tšoanang tsa orbitofrontal, preortalal cortex, le hippocampus ho lemaletse ho sebelisa mehlala ea liphoofolo li se li qalile ho bonts'a bofokoli bo bong bo bontšitsoeng lithutong tsa batho. K'hok'heine e laoloang ke ngaka e hlahisitse mathata a ho ithuta hape (mosebetsi oa pele oa hlooho) literekeng le litšoene (Jentsch et al a, 2002; Schoenbaum et al a, 2004; Calu et al a, 2007). Mohlomong ebile e le ho qobellang le ho feta, liphoofolo li lumelletse ho fihlella ka nako e telele, empa li sa fihlellehe, ho sebelisa koae ho bontšitse bofokoli ba ts'ebetso ea ho hopola (mosebetsi o itšetlehileng ka cortex), mosebetsi o hlokometsoeng (mosebetsi o tsepamisitsoeng pele ho cortex), le mosebetsi oa ho amohela ntho (mosebetsi o itšetlehileng ka hippocampus; Briand et al a, 2008a, 2008b; George et al a, 2008). Phuputsong e le 'ngoe (Briand et al a, 2008a), liphokotso tsena li ne li amana le ho fokotseha ho hoholo ha dopamine D2 receptor mRNA ka har'a cortices ea medical and orbital, e hlokometsoeng e boetse e lumellana le lithuto tsa batho ba nahanang. Kahoo, lithuto tsa liphoofolo tse sebelisang mefuta ea taolo e khothalletsang e khothalletsang li se li qala ho bonts'a bofokoli bo amanang le ts'ebeliso ea lithethefatsi tsa batho ba koae (bona lithuto tsa Batho: imaging le neuropsychopharmacology).
DITLHAKISO TSA BOPHELO: HO FIHLELA LE HO FIHLELA NECOPSYCHOPHARMACOLOGY
Joalokaha ho hlokometsoe ka holimo, bopaki bo tsoang lipatlisisong tsa tlhahlobo ea peleho le tliliniki bo fana ka maikutlo a hore temallo e emela li-neuroadaptations tse latellanang. Ka lebaka leo, ketso e qobelloang ea pele e fetoha ntho e qobelloang 'me e ba (qetellong) e sa foleng le e khutlang hape. Mosebetsi ho tsoa lithutong tsa ho nahana ka litšoantšo o fane ka bopaki ba hore phetoho ena e kenyelletsa ho pheta-pheta ha li-circonal tsa neuronal tse sebetsang (1) moputso le tšusumetso; (2) mohopolo, boemo le boemo; (3) ts'ebetso ea botsamaisi le taolo ea inhibitory; (4) ho buisana le ho itlhokomela; le (5) reactivity ea khatello. Phetoho ena e susumetsoa haholo ke liphatsa tsa lefutso, tsoelo-pele le tikoloho le tšebelisano ea bona e matla, e tla khetholla 'nete le ho teba ha temallo.
Hoa tšoana le lipatlisiso tse entsoeng pele ho nako, ho khetholla methati e meraro molemong oa ho lemalla joala ho batho (botaoa, ho tlohela, le ho lakatsa / ho oela hape) ho bile molemo. Likarolo tse latelang li hlalosa methati ena le tse ling tsa mekhahlelo e amanang le methapo ea kutlo eo li tsamaeang ka eona.
Binge / Mofuta oa Intoxication
Maemo a mangata a ho lemalla a hlahisoa ke tlhekefetso ea lintho tse batloang ka lebaka la thepa ea tsona ea hedon. Leha ho le joalo, teko ea lithethefatsi e boetse e hlaha litlamorao tse matlafatsang tsa ho lumellana le lihlopha tsa sechaba (khatello ea lithaka) ka phetiso e latelang ea ts'usumetso ea ho nka moriana ka litlamorao tsa oona tse matlafatsang. Khafetsa, ts'ebeliso ea pele ea lithethefatsi e kanna ea amana le thepa ea eona ea kalafo (joalo ka li-analgesics tsa opiate bakeng sa bohloko kapa li -vuser tsa khatello ea kelello e fokotsang tlhokomelo). Joalokaha ho bontšitsoe ke lithuto tsa preclinical, karolo ea bohlokoa ea litlamorao tse matlafatsang tsa lithethefatsi e amoheloa ka bophara ho kenyelletsa bokhoni ba bona ba ho baka keketseho e kholo ea extracellular dopamine libakeng tsa limbic (ho kenyelletsa le li-nucleus accumbens). Le ha ho ipusa ho lithethefatsi ho le boima ke mohlala o motle oa phoofolo bakeng sa tahi ea lithethefatsi, ho sebelisa mefuta ea liphoofolo ho hlahloba litekanyetso tsa tlatsetso ea dopamine tse tlisoang ke lithethefatsi ho thata. Lithuto tsa monahano oa Brain bathong li thusitse haholo ho bonts'a keketseho e tlisoang ke lithethefatsi ho dopamine ho striatum (ho kenyelletsa le ventral striatum moo li-nucleus accumbens li leng teng) li amahanngoa le litlhaloso tse mabapi le moputso (mohlala, thabo, phahameng, euphoria; Volkow et al a, 1996b). Ntle le moo, lithuto tsena li bonts'itse hore liphetoho tse potlakileng tsa dopamine li amahanngoa le pono e hlakileng ea moputso, athe keketseho e potlakileng le e tsitsitseng ea dopamine ha e hlahise likarabo tsena tse ikhethileng (Mosa, 2000; Volkow le Swanson, 2003).
Melemo ea litlhare tsa lithethefatsi, tse susumetsang lebelo la ho fihla kapele bokong le nako ea liketso tsa bona, ke likarolo tsa bohlokoa tsa bokhoni ba bona ba ho lemalla. Thepa ea pharmacokinetic e lekola litekanyetso, mekhoa ea tsamaiso, le khafetsa tšebeliso ea lithethefatsi kahare ho karolo e fanoeng. Mohlala, papiso ea boko pharmacokinetics ea cocaine le methamphetamine e senola hore ka bobeli ba fihla bokong ka potlako haholo (le ha cocaine e batla e potlakile ho feta methamphetamine) empa cocaine e tsoa bokong ka potlako haholo ho feta methamphetamine (Setšoantšo sa 3). Phapang ena e thusa ho hlalosa hore na hobaneng koae e sebelisoa ka mong le e mong 30-60motsotsoana nakong ea ho itlopa lijo, athe methamphetamine e nkuoa lihora tse ling le tse ling (Fowler et al a, 2008). Bohlokoa ba pharmacokinetics bo boetse bo thusa ho hlalosa hore na hobaneng lithethefatsi tse ngata tse hlekefelitsoeng (ntle le joala) li kenngoa, li tsuba, kapa li sa tsubeloe. Litsela tsena li lumella ho tlisoa ha moriana o potlakeloang bokong ho feta ha ho nooa ka molomo (Volkow et al a, 2000). Pharmacokinetics e boetse e thusa ho hlalosa hore na hobaneng lithethefatsi tse khothalletsang tse kang methylphenidate kapa amphetamine, tseo le tsona li eketsang dopamine, ha li nkuoe hangata e le matlafatso ha li nkuoa ka molomo joalo ka ha li laetsoe kalafo (Etsa, 1994; Volkow et al a, 2001b).
Liphuputso tsa bongaka li boetse li bontšitse hore tebello ea litlamorao tsa sethethefatsi e susumetsa haholo likarabo tse khahlisang tsa lithethefatsi, joalo ka hore boits'oaro le boits'oaro ba ts'ebetsong ba ts'ebetso ea bokong ho lithethefatsi bo ba matla haholo ha ho lebelletsoe setlhare se putsang ha se bapisoa le ha sethethefatsi sona seo se amoheloa ka mokhoa o sa lebelloang (Volkow et al a, 2003). Ho itšetleha ha litlamorao tse khahlisang tsa setlhare ho latela maemo le tebello ho fana ka maikutlo a bohlokoa ba li-neurotransmitters tse ling tse kang glutamate, e tsamaisang ts'ebetso ea lisele tsa dopamine le ho lokolloa ha dopamine ka har'a li-nucleus accumbens, litlamorao tse ntle tsa lithethefatsi tsa tlhekefetso (Kalivas le Volkow, 2005).
Withdawal / Boemo bo Fosahetseng ba Boemo
Karabelo e latelang mohato oa botaoa ba lithethefatsi e fapana haholo lithethefatsing mme e susumetsoa ke ho sa feleng le khafetsa ha tšebeliso e mpe ea lithethefatsi. Bakeng sa lithethefatsi tse ling tse kang li-opiates, joala le hypnotics e thetsang, ho khaotsa lithethefatsi ho basebelisi ba lithethefatsi tse sa foleng ho ka baka lefu le matla le matla la ho khaotsa 'mele, haeba le sa laolehe hantle le ha le le matla, ka linako tse ling le ka bolaeang. Litlhare tsohle tsa tlhekefetso li amahanngoa le lefu la ho tlohela 'mele le bonts'ang ho kula, ho teneha, khatello ea maikutlo, le likhathatso tsa boroko tse phehellang esita le kamora ho khaotsa ho tsubang. The neurobiology ea ho tlohela ka matla ke phapang e tsoang ho motho ea ikemiselitseng ho tloha kapa ea susumetsang, 'me ka bobeli ba kenya letsoho ho oeleng hape. Ho se ho entsoe lithuto tse fokolang tsa monahano nakong ea ha motho a tlohela haholo. Phuputso e 'ngoe e joalo e lekantseng liphetoho tsa dopamine nakong ea ho tlosoa ha heroin e ile ea sitoa ho tiisa hore dopamine e fokotseha ka har'a li-nucleus tse bokellaneng tseo ho neng ho tlalehiloe ka ts'ebetso ea microsalysis bokong ba methapo (Wang et al a, 1997). Ho tsoa thutong ena, ha ho hlake hore na sephetho se bontša ho se amehe ha dopamine ea striatal nakong ea ho khaola ho matla ho bahlaseli ba heroin kapa maikutlo a fokolang a theknoloji ea positron emission tomography (PET).
Mekhoa ea ho tlosa ka mokhoa o matla e kanna ea ba lithethefatsi tse itseng mme e bonts'a liphetoho liphekellong tsa limolek'hule tsa lithethefatsi tsena. Mohlala, matsatsing a 'maloa a pele a ho khaotsa koae, ho utloahala ha kelello ho amang litlamorao tsa lithethefatsi tse ntlafatsang tsa GABA hoa etsahala ho ka bontšang ho fokotseha hoa neurotransmitter ena ka tšebeliso e sa foleng ea koae (Volkow et al a, 1998). Ka mokhoa o ts'oanang, lithuto tsa ho nahana ka boko li boetse li senotse ho fokotseha ha li-opioid tsa nako ea tlhaho nakong ea ho khaotsa koae, tse ka bakang ho teneha, malaise le dysphoria tse etsahalang nakong ena ea karolo ea khothalletso ea ho tlohela (Zubieta et al a, 1996).
Nakong ea ho khaotsa ho neng ho se ho entsoe, hang ha matšoao le matšoao a ho khaohana ka matla a se a kokobela, lithuto tsa ho nahana ka litšoantšo li tlaleha hypofunction litseleng tsa dopamine, tse bontšitsoeng ke ho fokotseha ho D2 polelo ea receptor le ho fokotseha ha tlhahiso ea dopamine, e ka kenyang anhedonia (ke hore, ho fokotseha ha maikutlo ho susumetso e khotsofatsang) le khaello ea litheko tse tlalehiloeng ke liithuti tse lemaletseng lithethefatsi nakong ea ho khaotsa ho tsoelang pele (Volkow et al a, 1997b, 2007; Martinez et al a, 2004, 2005). Reactivity e fokotsehileng ea dopamine ho matlafatsa maikutlo e boetse e ba teng ka mor'a ho khaotsa ho ts'ebeliso ea joala ha ho itlopa ka matla ho se ho theohile. Ho fapana le maikutlo a fokotsehileng a meputso (ho kenyeletsa le meputso ea lithethefatsi), lithuto tse inahaneloang li tlalehiloe hore nakong ea ho nats'oa lihlahisoa tsa 'mele, ntlafatso ea maikutlo ho li-cues tse nang le maemo le tsona lia etsahala. Ho tlohela ho tsuba, ho etsa mohlala, ho ka baka karabelo e makatsang mokhoeng oa tlhaho ho litloaelo tse amanang le ho tsuba (McClernon et al a, 2009). Likarabo tsena tse nang le maemo li boloka mokhoa oa ho ila le ho khutla hape o tšoaeang mathata a ts'ebeliso ea lithethefatsi (Ho ba le bana et al a, 1988).
Ntle le moo, liphuputso tse nahannoeng tse sebelisang matšoao a ts'ebetso ea boko li bonts'itse hore basebelisi ba lithethefatsi ba ileng ba lekoa nakong ea litheko tse ntlafalitsoeng ba bonts'a bopaki ba ts'ebetso e sitisitsoeng ea libaka tse ka pele, ho kenyelletsa le libaka tsa pele tsa dorsolateral, cingrate gyrus, and orbitof Pambal cortex, e khothalletsoang hore e theole taolo ea bona e senyehileng ea taolo le ho susumetsa le ho kenya letsoho ho khutla hape (bona karolo e latelang bakeng sa lipuisano).
Preoccupation / Ketso ya ho lebella (ho lakatsa) Mothati
Kutloisiso e ntlafalitsoeng ea litloaelo tse boemo bo botle, tse kenyelletsang maikutlo a maikutlo, e tsosa mohopolo oa morao-rao oa ho nahanisisa / ho lebella (ho lakatsa), o bonts'ang ke keketseho ea takatso ea lithethefatsi. Ho joalo, khatello ea maikutlo ke sesosa se matla sa ho khutlela mekhoeng ea ho ts'oara lithethefatsi ka ts'ebetso ea liserekisi tsa boko tse kenyelletsoang ts'ebetsong ea meputso le tlhokomelong e khahlisang le ea monontsa bakeng sa likhopotso tsa tšebeliso ea lithethefatsi (Duncan et al a, 2007). Ketsahalo ena e sa feleng ea ho khutlela morao e tsejoa e le e 'ngoe ea mathata a thata ho loants'eng lithethefatsi. Baithuti ba lemaletseng tlhekefetso ba tlameha ho khutlela ho tšebeliso e mpe ea lithethefatsi kamora nako e telele ba le matšoao a ho tlohela ka boqhetseke (Langleben et al a, 2008). Ho hlophisoa hanyane ka hanyane ha moputso le likarete tsa ho hopola, tse tlisoang ke ts'ebeliso e mpe ea lithethefatsi, li khothaletsoa ho ba tsa bohlokoa likarolong tsena tsa likarabo tsena. Ka bobeli dopamine le glutamate li fumanoe lithutong tsa preclinical e le tse tlatsetsang phetohong ea neuroplastic e amanang le likarabo tse nang le maemo. Ho feta moo, liphetoho tsa polasetiki ho CRF le li-glucocorticoid receptors li ka nka karolo botebong ba kutlo bo ntlafalitsoeng ba khatello. Ho batho, ho haella ha li-radiotracers tse loketseng ho hlahloba li-glotamate neurotransication le ho haella ha li-ligands bakeng sa li-CRF kapa glucocorticoid receptors li fokolitse lithuto tsa ho lakatsa boholo ba sistimi ea dopamine.
LIT DOBOTSI TSA BOPHELO BA NEUROCIRCUITRY KE HO FIHLA BOPHELO
Neurocircuitry e boletsoeng ka holimo e theha motheo oa neuroplasticity e amanang le nts'etsopele ea bokhoba ba tahi. Kakaretso e ka tlase ke liphetoho tse etsahalang kahare ho lipotoloho tse emelang mehato ea potoloho e boletsoeng ka holimo. Li-circuits tse hlano li na le maikutlo a ho kenella ka tatellano, ho kenyelletsa (1) mesolimbic dopamine system, (2) ventral striatum, (3) li-circral striatum / dorsal striatum / thalamus circuits, (4) dorsolateral frontal cortex / inferior frontal cortex / hort le (5) amygdala e atolositsoeng (Setšoantšo sa 4). Boima le tataiso ea liphetoho tse amanang le liphetoho tsena li bontšoa setšoantšong sa potoloho ea naha e lemaletseng (Setšoantšo sa 5).
Sistimi ea Mesolimbic Dopamine: Mekhoa ea Motlatsi oa Salience, Attribution ea Salience
Mohopolo o mong o ka sehloohong o tataisang neuroplasticity e amanang le ho lemalla o tsepamisitse maikutlo ho sistamine ea mesolimbic dopamine. Khopolo-taba ke hore lithethefatsi tsa tlhekefetso, haholo cocaine le amphetamine, li eketsa tokollo ea dopamine ka mokhoa o tšoarellang le o sa laoloang ho feta ts'usumetso ea tlhaho, e bakang liphetoho lipolitiking tsa synaptic kahare ho sistimi ea dopamine le li-neuroprotic tse amohelang dopamine (Wolf, 2002). Liphetoho tsena li etsa hore mekhoa e tloaelehileng ea ho ithuta e fetohe mokhoa oa ho ithuta ka methapo kapa mokhoa oa ho ithuta o phehellang ha o tobane le litlamorao tse mpe (karolo ea ho qobelloa. Everitt le Wolf, 2002; Hyman et al a, 2006).
Mefuta ea liphoofolo ea maikutlo a boits'oaro e tsepamisitse maikutlo ho litlamorao tse matlafatsang tsa litla-morao tsa psychomotor e matla ho liphoofolo tse nang le nalane ea ho pepeseha. Lithuto tse joalo li senoletse neuroplasticity e ngata e amanang le litsamaiso tsa mesolimbic dopamine le projeke ea eona ea terminal ho ventral striatum (moo li-nucleus accumbens li leng teng). Lithethefatsi tsa tlhekefetso li baka phetoho ea nakoana le ea nako e telele ea ho thunya ha methapo ea methapo ho dopamine ho VTA (Bonci et al a, 2003). Boithuto bo bontšitse hore ho phatloha ho matla ha dopamine neurons ho VTA ho bonahala ho hokahanngoa le karabelo e lebisang ho tšusumetso ea maikutlo (Freeman et al a, 1985). E le 'ngoe Ka vivo ho pepesehela cocaine kapa amphetamine ho etsa hore ho be le nako e telele ea potentiation (LTP) ea li-neurotransication tsa AMPA-mediated e thabisang ho li-dopamine neurons (Nts'a et al a, 2001). Monyetla oa likarabo tsa synaptic AMPA o tšellelitsoe ho eketsa menyetla ea ho thunya ho hoholo (Jones le Bonci, 2005). Tlhokomelo e tšoarellang ea nako e telele ea likhoeli tse 3 ea ho itlhatsoa e kentsoe ho VTA ka likhoto tse sebelisang koae ka mafolofolo empa e se ka litekong tse kenang ka mokhoa o ikhethileng (Chen et al a, 2008). Litlamorao tse ts'oanang tsa ho kenyelletsoa ha EPP ea phetisetso ea glutamate ho dopamine neuron li hlokometsoe ka morphine le nicotine (Etsahale et al a, 2003).
Leha ho le joalo, taolo e pheta-phetoang ea psychostimulants e sa atleha ho hlahisa ts'ebetso ea mesolimbic dopamine joalo ka ha e lekantsoe ke Ka vivo microsalysis (Maisonneuve et al a, 1995). Ntle le moo, phihlello e atolositsoeng ea koae e sitoa ho hlahisa sensomization ea locomotor (Ben-Shahar et al a, 2004) empa e hlahisa karabelo ea boitšoaro bo sa rateheng (Ferrario et al a, 2005). Ho feta moo, batho ba hlekefetsang batho ba koae ka koae ba bonts'a likarabo tsa dopamine tse fumanoeng ha ba qholotsoa ka moriana o hlasimollang, o khahlano le o boletsoeng ke ts'usumetso e matla ea mosebetsi oa mesolimbic dopamine (Volkow et al a, 1997b; Martinez et al a, 2007).
Ventral Striatum: Kholiseho ea Salience Pathways, Salience Attribution
Plastiki e 'ngoe e amanang le tšusumetso ea boits'oaro ke ts'ebetso e phehellang ea li-nucleus e bokellanang li-synapses tse bonoang ka mor'a ho pepesetsoa lithethefatsi khafetsa tse lateloang ke nako e atolositsoeng ea lithethefatsi (Kourrich et al a, 2007). Tsamaiso ea koae e phetoang khafetsa e eketsa glutamate neurotransication feela ho likhoto tse bonts'itseng maikutlo a boitšoaro (Pierce et al a, 1996). Ntle le moo, litoeba tse khothatsang koae li bonts'itse ntlafatso ea ts'ebetso ea LTP litekeng tsa nucleus e bokellanang nakong ea ho ikhula, ka mokhoa o hlakileng e bonts'a ts'ebetso e eketsehileng ea ts'ebetso ea glutamatergic (Yao et al a, 2004). Tekanyo e eketsehileng ea bokaholimo ba li-receptor tsa glutamate-1 (GluR1) e 'nile ea bonoa matsatsing a 21 kamora ho ts'oaroa ha jekeng ea ho qetela ea koae, e fana ka maikutlo a hore butle-butle ho ajoa li-receptor tsa AMPA butle-butle ka holim'a li-neuron tsa rubus, haholoholo ho tse se nang GluR2 (Boudreau le Wolf, 2005; Conrad et al a, 2008). Keketseho ea li-receptor tsa AMPA tsa selefouno ho latela ts'ebetso ea dopamine D1 li-receptors le protheine tse latelang tsa kinaseChao et al a, 2002). Ka mokhoa o sebetsang, ho tšetšetha ho ho feteletseng ha GluR1 ka har'a nucleus ea ho bokella ho nolofalitse ho felisoa ha likarabo tse batlang koae (koae)Sutton et al a, 2003) le likotsi tse eketsehileng tsa moputso oa ts'ebetso ea ts'ebetso ea kelello, ho bonts'a moputso o fokotsehileng mme mohlomong le ho fokotsa boitšoaro bo susumetsang (Todtenkopf et al a, 2006). Leha ho le joalo, ho pepesetsoa le koae hape ka nako e le 'ngoe ha motho a khaotsa ho tsuba ho hlahisitse khatello ea maikutlo, e ka bonts'ang tokollo e ntlafalitsoeng ea glutamate nakong ea ho hlakoloa ha koae (Kourrich et al a, 2007). Ka mokhoa o makatsang, keketseho ea polelo ea li-receptor ea AMPA e bonoang le cocaine ha e etsahale ho litoeba tse ammettamine tse lebisang ho hypothesis ea litlamorao tse fapaneng tsa tšebetso ea likhakanyo tsa glutamate ho li-nucleus accumbens nakong ea k'hok'heine vs Ho khahlisoa ke amphetamine (Nelson et al a, 2009).
E lumellana le sephetho sa phetoho e fetotsoeng ea "glutamate neurotransication" lithutong tse nang le maikutlo a cocaine, tlhahlobo ea Microphilia le microinjection li bonts'itse hore kamora 'cocaine e sa foleng, ho theoha ha tokollo ea glutamate empa hoa utloahala ha ho kopants'oa glutamate ha ho khutlisoa ho batla lithethefatsi litekong (Kalivas le O'Brien, 2008; McFarland et al a, 2003). Tekanyetso ena ea glutamate e anngoe hore e bakoe ke ho fokotseha ha ts'ebetso ea cystine-glutamate exchanger (Baker et al a, 2003) le takatso ea methapo ea metabotropic glutamate mGlu2 / 3 receptor. Tekanyo e tlase ea basal glutamate, e kopantsoeng le ho eketsoa ha glaptamate ea synaptic ho tloha ts'ebetsong ea litumellano tsa pele tsa cortex ho li-nucleus accumbens, li hlahisoa ka sepheo sa ho etsa hore ho be le ts'ebetso ea ho batla ts'ebeliso ea lithethefatsi (Kalivas, 2004).
Litlamorao tsena tsa nako e telele tsa synaptic li hlahisa ho fokotseha ha glutamate neurotransication nakong ea taolo e sa fetoheng ea lithethefatsi le keketseho e tsitsitseng ea ts'ebetso ea glutamatergic synaptic neurotransmission nakong ea ho khutla kamora ho tlosoa. Liphetoho tsena tse matla li ka khothaletsa boitšisinyo ba sethala, bo pakiloeng hore e be karolo ea bohlokoa bakeng sa ho susumetsa maikutlo le thuto e amanang le lithethefatsi maemong a ho lemalla (Kauer le Malenka, 2007; phiri et al a, 2004).
Joalokaha ho khothalelitsoe ke mehlala ea liphoofolo, boholo ba matla a ho lokolloa ha striatal dopamine (haholo maemong a eona a ka hare) bathong bo lumellana hantle le karabelo ea hedonic ho lithethefatsi tse ngata tsa tlhekefetso, ho kenyeletsoa le amphetamine (Litokiso et al a, 2001), cocaine (Volkow et al a, 1997a), methylphenidate (Volkow et al a, 2002), le nicotine (Sharma le Brody, 2009). Phapang e atamelitsoeng ke lithethefatsi, e potlakileng, le ea maemo a holimo ho dopamine e ka etsahalla liphetoho tsa dopamine tse hlahisoang ke phasic dopamine cell firing e etsahalang ka lebaka la ts'usumetso e kholo, ka hona, ho hlophisa boiphihlelo ba lithethefatsi e le bo ikhethang haholo, sephetho se fumanoeng O laela tlhokomelo mme o phahamisa ho tsosa, ho ithuta ka mokhoa o hlophisehileng, le khothatso (Volkow et al a, 2004b). Motheong oa liphumano liphoofolong tsa laboratori, ho pepesetsoa khafetsa likarabo tsena tsa lithethefatsi ho batho ba sebelisang lithethefatsi hampe ho tsamaisoa ka sepheo sa ho khutlisa likotlo tse tlisoang ke dopamine-activating (moputso) bakeng sa litlatsetso tsa tlholeho.
Kahoo, motho a ka nahana nts'etsopele ea phetoho ea ho thunya ho mesolimbic dopamine neurons e qalang ka taolo e le 'ngoe ea lithethefatsi, e qala ho ba EPP ka lekhetlo la pele ho VTA ebe li-nucleus li bokellana,' me ka mela ea melaetsa ea morao-rao li kenya tšebetsong ea dorsal striatum. Ho feta moo, liphetoho tsa nako e telele ho CeA le medial prefrontal cortex li ka latela, mme li kopantsoe le taolo ea methapo ea khatello ea kelello (bona ka tlase) e ka fana ka ts'usumetso e matla bakeng sa boits'oaro ba ho batla lithethefatsi esita le likhoeli kamora ho tlosoa hoa lithethefatsi (Setšoantšo sa 4 'me and55).
Ventral Striatum / Dorsal Striatum / Thalamus: Ka boithaopo ho tloaelo ea ho sebelisa lithethefatsi
Hypothesis e reng dorsal striatal circry e na le karolo ea bohlokoa ntlafatsong ea tšebeliso ea koae e phehellang e ts'ehetsoa ke datha e bonts'ang bohlokoa ba dorsal striatum ho ts'usumetso ea ts'usumetso ea karabelo-Che et al a, 2005) le lithuto tsa Microbalalysis tse bonts'ang hore ho batlana le koae ka nako e telele ho eketsa ho lokolloa ha dopamine ka dorsal striatum empa eseng ventral striatum (Ito et al a, 2002). Ho khaoloa ha ventral striatum ho tsoa ho dorsal striatum ho likhoto tse itšebetsang k'hok'heine ka tatellano ea tatellano ea bobeli ho bonts'a khaello ea liphoofolo tse nang le tlhahiso e tiileng ea 'qobello' empa eseng ho liphoofolo tse sa tsoa fumana lenane la tatellano ea bobeli (Belin le Everitt, 2008). Kahoo, khopolo-taba ke hore bokhoba ba lithethefatsi bo emela liphetoho meahong e amanang le bona hore e be tse iketsahallang kapa tse tloaelehileng 'me li kenyelletsa boitlamo ba butle-butle ba dorsal striatal methane.
Liphuputso tsa liphoofolo li khothalelitse ka matla hore ka ho pepesetsoa lithethefatsi khafetsa tse amanang le sethethefatsi, qetellong li ka ba le bokhoni ba ho eketsa dopamine ka bo tsona. Lithuto tsa monahano oa Brain li netefalitse sena ho batho ba lemaletseng (Volkow et al a, 2008a; Heinz et al a, 2004). Lithuto tsena li bonts'itse hore litso tse amanang le lithethefatsi li susumetsa dopamine ho eketseha ha dorsal striatum (caudate le putamen), phello e amanang le litlaleho tsa boithati tsa ho lakatsa. Taba ea hore boholo ba dopamine e eketseha bo bakiloeng ke likhakanyo li ne li amahanngoa le tekanyo ea bokhoba ba tahi e totobatsa bohlokoa ba likarabo tsa dopamine tse maemong a ts'ebetsong ea ts'ebeliso ea lithethefatsi ho batho.
Boithuto ba tsa bongaka bo boetse bo bonts'itse hore dopamine e liehang ho thella e eketseha ka lebaka la taolo e matla ea methylphenidate ea molomo ha e khothalletse ho hlekefetsoa ha batho ba hlekefetsang koae ntle le hore e tsamaisane le litheko tse amanang le lithethefatsi.Volkow et al a, 2008a). Sena se kanna sa bonts'a 'nete ea hore litakatso tse tsoang ho dopamine e potlakileng li eketseha ka ho thunya ha phasic dopamine, ho fapana le keketseho e potlakileng ea dopamine e fumanoang ka ho thunya hoa tonic le litekong tsa methylphenidate ea molomo. Ebile, tsamaiso e kenelletseng ea methylphenidate, e hlahisang ho eketseha ha dopamine ka potlako, e etsa hore motho a be le takatso e matla.
Boithuto ba ho nahana ka Brain bo boetse bo bonts'itse hore, lithutong tse lemaletseng lithethefatsi, lits'ebetso tsena li kenyelletsa orbitofrontal cortex, sebaka sa boko se kenyelletsoeng seseng sa tšusumetso le tšusumetso, pherekano e bakoang ke ho qobelloa, hape ke sebaka sa boko se nang le lipakanyo tse matla ho dorsal striatum . Gingus ea cingulate e boetse ea ameha 'me ke karolo ea boko e kentsoeng taolong ea thibelo le tharollo ea likhohlano, e leng pherekano e hlahisang ho se tsitse (Volkow et al a, 2004b). Ntle le moo, ho lithethefatsi tsa koae, empa li sa thibeloe, lihlooho, tsamaiso e kenelletseng ea methylphenidate, eo ba hlekefetsang koae e fanang ka litlamorao e ts'oanang le ea koae, ba kenya ts'ebetso ea cortices ea orbital le ea mori, mme ts'ebetso ena e ne e amana le takatso ea koae.Volkow et al a, 2005). Ka mokhoa o ts'oanang lithutong tse lemaletseng matekoane a boloi, empa eseng ho batho ba sa lumelloang ke molao, tsamaiso e matla ea Δ9-THC e sebelisitse cortex ea obitofrontal (Volkow et al a, 1996a). Ts'ebetso ea "citex" ea obitof Pambal le gingus e boetse e hlohlelletsoa ke mekhoa e lemalloang e bolelang moputso le litakatso tsa pele (McClernon et al a, 2009). Ho khahlisang, tsena ke libaka tse laolang ho fokotseha ha sele le ho lokolloa ha lisele, tse 'nileng tsa hlahisoa ho hlokahala bakeng sa litekanyetso tse ntlafatsang tsa tšusumetso ea lithethefatsi ho batho ba lemaletseng (ho beha khalase e thehiloeng lithutong tsa liphoofolo; Volkow et al a, 1999). Ha li kopantsoe, lipatlisiso tsena li tiisa ka tieo hore keketseho ea dopamine e amanang le mekhoa ea boemo bo botle ha se likarabo tsa mantlha, empa ho fapana le hoo, sephetho sa tlhahiso ea maikutlo ea lisele tsa dopamine, e ka etsahala haholo liphatlalatsong tsa glutamatergic tse tsoang cortex ea pele le / kapa amygdala. Motheong oa liphumano tsena, ts'ebetso ea obitofrontal cortex, le keketseho e kopanang ea dopamine e hlahisoang ke moriana, e kentsoe hypothesed ho kenya letsoho ts'ebelisong e matla ea lithethefatsi e khethollang batho ba lemaletseng lithethefatsi (Volkow et al a, 2007).
Ho joalo, lithuto tsa neuroimaging tsa batho li bonts'a hore pele-pele cortex (orbitof Pambal, medial prefrontal, prelimbic / cingulate) le basyatal amygdala li bohlokoa haholo takatsong ea litheko le litakatso tsa batho.Franklin et al a, 2007). Libakeng tse ka pele (mohlala, cingrate gyrus le obitofrontal cortex), liphetoho tsena li amahanngoa le phokotso ea dopamine D ea striatal dopamine D2 fumaneha ka bongataHeinz et al a, 2004; Volkow et al a, 1993, 2001a, 2007). Mekhatlo ena e kanna ea bonts'a tšitiso ea likarolo tsa bokapele ba kapele ho liphetoho mesebetsing ea dopamine kapa ka mokhoa o mong li ka supa tšitiso e ka sehloohong ea libaka tse ka pele tse laolang tšebetso ea sele ea dopamine. Ho joalo, phuputso ea morao-rao ea PET e fane ka bopaki ba hore libaka tsa bokong tsa pele li laola boleng ba meputso ka ho fetolela keketseho ea dopamine ho ventral striatum, mochine oa taolo o fetoha o sa sebetseng ho batho ba lemaletseng (lithethefatsi).Volkow et al a, 2007).
Ka hona, dopamine e kopanetsoeng le phepelo ea glutamate ho dorsal striatum, e leng sebaka se kenyelletsoeng ho ithuteng tloaelo le ho qala ketso, se ameha takatsong e itšetlehileng ka cue / moelelo oa taba. Kahoo, dorsal striatum e kanna ea ba karolo ea mantlha ea bokhoba ba tahi (Volkow et al a, 2006). Patlisiso mabapi le maano a manyane a ho thibela dopamine ea boemo bo holimo le likarabo tsa glutamate ke sepheo sa mantlha sa boiteko ba hona joale ba ntlafatso ea meriana.
Thalamus ha e so ithutoe haholo molemong oa temallo. Leha ho le joalo, ka lebaka la ts'ebetso ea bona e amanang le taolo ea ho feto-fetoha ha maikutlo a monate le a tlhokomelo, sebaka sena se bile le tšusumetso e matla tšebetsong ea bokhoba ba tahi. Mohlala, tsamaiso e kenelletseng ea sethethefatsi se susumetsang ho batho ba hlekefetsang koae, empa eseng ka taolo, e ile ea eketsa dopamine neurotransuction ho thalamus, phello e amanang le ho lakatsa (Volkow et al a, 1997a). Ka lehlakoreng le leng, ha ho bapisoa le taolo, ba hlekefetsang koae ba bonahatsa hypoactivation ea thalamus, mohlomong e bonts'a bofokoli ba noradrenergic le / kapa dopaminergic, ha ba etsa mosebetsi oa ho lemoha (Tomasi et al a, 2007b). Ka mokhoa o ts'oanang, thalamus e tlalehiloe e bonts'a ts'ebetso e bonts'itsoeng ha e ntse e etsa mosebetsi o bonoang oa bonohe ho ba tsubang ba pepesetsoeng nicotine (Sharma le Brody, 2009). Liphetho tsena li fana ka maikutlo a hore tlhekefetso ea thlamic ho batho ba hlekefetsang koae e ka keke ea kenya letsoho ho sitiseng ts'ebetso ea maikutlo le tlhokomelo empa hape le ho lakatseng. Ho khahlisang, liphetoho phetisong ea dopamine ho thalamus le striatum li bonahala li ameha ho senyeheng ha ts'ebetso ea kelello (mohlala, tlhokomelo ea pono le mohopolo oa ho sebetsa) o latelang ka mokhoa o sa tsotelleng nako ea ho hloka boroko (Volkow et al a, 2008b). Kahoo, lipatlisiso tse ling tse thehiloeng holim 'a tlhaiso-leseling e fumanehang li loketse.
Dorsolateral Frontal Cortex, Infort Frontal Cortex, Hippocampus: Taolo ea Kelello, Thibelo ea ho lieha, le Memori
Ho lemalla ho boetse ho kenyelletsa litšebelisanong tsa kelello le tsa maikutlo tse laoloang ka mokhoa o laolehileng, tse bakang ho tlatlapuoa ho matlafatsang ha lithethefatsi ka litšenyehelo tsa ho sitisoa ha litlatsetso tsa tlholeho, le bofokoli taolong e thibelang likarabo tsa lithethefatsi (Goldstein le Volkow, 2002). Ka lebaka leo, sistimi e sa sebetseng hantle e pele e lumeloa hore e bohlokoa molemong oa ho lemalla.
E 'ngoe ea likarolo tsamaisong ena ke taolo ea litšusumetso, e leng e' ngoe ea lisosa tse kotsi tsa ts'ebeliso ea ts'ebeliso ea lithethefatsi. Cocaine e bonahala e na le phello e tobileng ho neurobiology e tlasa taolo ea ts'usumetso. Kamora ho kenngoa ka har'a ente ea koae, basebelisi ba koae ba hlile ba bontšitse ntlafatso mosebetsing oa thibelo ea makoloi 'me ba kopane le ts'ebetso e nepahetseng e kenelletseng kahare ea bona e nepahetseng ea dorsolateral le inferior ea frontal (Sekepe et al a, 2008). Hobane libaka tsena li nkuoa e le tsa bohlokoa taolong ea tšusumetso ea batho, ts'upiso ena e fana ka maikutlo a hore litlamorao tse mpe tsa koae li hlile li ka kopanya phetoho ea nakoana ea ts'ubuhlellano e sa feleng ea taolo ea nakoana.
Ts'ebetso e 'ngoe ea bohlokoa e lulang libakeng tsa frontocortical ke bokhoni ba ho khetha pakeng tsa moputso o monyane le oa hang hang ha o bapisoa le moputso o moholo empa o fokotsoe, o ka lekantsoeng ho sebelisoa mosebetsi o liehang oa ho theola. Phuputso ea morao-rao e fumane hore bobeli ba dorsolateral and inferolateral frontal cortex gumex e lumellana ka mokhoa o fapaneng le khetho ea ho khotsofatsa hang ha ho etsoa liqeto (Bjork et al a, 2009). Phuputso ena e fana ka maikutlo a hore tlhekefetso libakeng tse nang le maemo a pherekano e ka baka ho sitoa ho lieha ho khotsofatsa, mokhoa o nang le ts'oaetso le bokhopo bo bong ba kelello.
Likarolo tse tlase tsa ho hopola le ho ithuta ka mokhoa o hlophisehileng ke tse ling tsa lipotoloho tse kholo tse sebetsanang le phetoho ha motho a qeta ho pepesetsoa lithethefatsi (Volkow et al a, 2004a). Ho kopantsoe mekhoa e fapaneng ea memori ea ho kenya letsoho ts'ebetsong ea lithethefatsi, ho kenyelletsa le maemo a ho ithuta a khothalletsang (ka li-nucleus accumbens le amygdala), ho ithuta ka tloaelo (ka caudate le putamen), le memori e fokotsang (ka hippocampus; Bosoeu, 1996), e leng eona ntlha ea karolo ena.
Lilemong tse leshome tse fetileng, lithuto tse ngata tsa liphoofolo tse tsosang takatso li khothalelitse hore lithethefatsi tse lemalloang li ka senya neurogeneis ho hippocampus ea motho e moholo.Kanales, 2007). Ho senyeha ha subralulum ea hippocampus ho ile ha bontšoa ho ama ho itaola ha koae ho likhoto (Caine et al a, 2001). Tlhahlobo e joalo e fane ka leseli la hore ho ka ba le monyetla oa ho kenya letsoho hippocampus e tsoileng taolong ea batho. Khopolo-taba ena ke katoloso ea tsebo ea hajoale hobane hippocampus e shebiloe e le ea bohlokoa maemong a maemo, e leng ts'ebetsong ea litekanyetso tse ka hopoloang ka likhopolo tse ka fumanoang ho tsona hape. Ebile, memori e fokolisang maikutlo esale e tsejoa e le khale ea ho nka karolo ho ithuteng le ho hokahanya maemo a amanang le maemo kapa maemo le boiphihlelo ba ho sebelisa lithethefatsi. Boithuto bo mabapi le PET le monahano o sebetsang oa matla a matla a sefahleho o bonts'itse hore takatso ea chue-elicited, hammoho le tahi e matla, e matlafatsa hippocampus le amygdala (Volkow et al a, 2004a). Mohlala, takatso eo basebelisi ba koae ba e fumanang ha ba pepesetsoa ts'usumetso e amanang le lithethefatsi e tsamaisana le ho eketseha ha phallo ea mali sebakeng se arolelitsoeng se amehang ka mefuta e mengata ea memori, ho kenyelletsa le amygdala (Ho ba le bana et al a, 1999; Grant et al a, 1996; Limil et al a, 2001) le hippocampus (Limil et al a, 2001).
Ka hona, mekhoa e mecha ea ho senya ts'ebetso ea memori e ka thusa ho felisa kamano e matla lipakeng tsa moelelo le lithethefatsi (Lee, 2008; lee et al a, 2005). Ho khahlisang, β-Blockers ba se ba bontšitse bokhoni bo ts'episang ba ho thibela likarabo tse nang le maemo ho li-reinforcers tsa tlhaho le bohlohlelletsi (Miranda et al a, 2003). Ho feta moo, liphetho tse tsoang phuputsong ea morao tjena li bonts'a hore likarabo tse tlisoang ke lithethefatsi le tsona li ka tsotella βkalafo -blockade (Milton et al a, 2008). Ka mokhoa o ts'oanang, lipatlisiso tse ling tsa lithethefatsi tse matlafatsang tsa GABA le tsona li bonahala e le mabaka. Ho hlohlelletsa ha GABAergic, ho ka fokolisang boemo ba Pavlovian, ho bonahala ho sitisa karabelo ho lithethefatsi tsa tlhekefetso ho liphoofolo (Volkow et al a, 2004a) hape e ka ba leano le sebetsang la ho phekola bokhoba ba batho (Dewey et al a, 1998).
Amygdala e Atolositsoeng: Mekhoa e Metle ea Matlafatso ea Matla
Tšebeliso e mpe ea lithethefatsi e hlalosoang ke ho ata ha lithethefatsi tse nang le phihlello e atileng e tsamaisana le tšitiso e sa feleng ea moputso oa boko homeostasis o sebelisa mehato ea menahano ea mehopolo ea bongo. Ho pepeseha ho fapaneng ha taolo ea lithethefatsi ho na le litlamorao tse kholo mollong oa moputso o ntseng o eketseha butle-butle (ke hore, moputso o fokotsehileng) phihlelong e atolositsoeng, empa eseng ka phihlello e fokolang, litekolo ho pholletsa le linako tsa tsamaiso ea tsamaiso e latelang (Ahmed et al a, 2002; Kenny et al a, 2006; Wee et al a, liphetho tse sa phatlalatsoang). Liphoofolo tse nang le phihlello e eketsehileng ea koaeine li ameha haholo ho thibelo ea boits'oaro ke bahanyetsi ba dopamine le bahanyetsi ba nakoana (Ahmed le Koob, 2004; Wee et al a, 2007), le lethalamo la agonist la karolo ea agonist e fapaneng ka ho fokotseha ka ho fokotseha ka boits'oaro ba heroin ka ho fihlella phihlello, litoeba tse itšetlehileng ka opioid (Chen et al a, 2006b), ho fana ka maikutlo a hore ho khutlisetsa bofokoli ba moputso ho ka senya sepheo sa ts'ebeliso ea lithethefatsi. Mochine ona o ka tlatsa molemo oa kalafo ea methadone le buprenorphine tšebelisong ea bokhoba ba heroin.
Joalokaha ho boletsoe kaholimo, bahanyetsi ba CRF ba thibetse litlamorao tse kang tsa ho natefeloa ke lithethefatsi le ho tlohela lithethefatsi tsohle tsa tlhekefetso tse entsoeng CRF ho CeA. Boitlhotlhollo bona bo lebisitse khopolong ea hore ts'ebetso ea CRF, ka kotloloho extrahypothalamic CRF ho CeA, e kentse letsoho ho khothaletso ea mmuso ho susumetsa ho tsoa ponong e mpe ea ho matlafatsa (Koob le Le Moal, 2008). Kahoo, motho a ka bolela esale pele hore mokhoa o fokolisang oa khatello ea kelello mekhoeng ea liphoofolo ea ho fihlella lithethefatsi o ka thibela tšusumetso ea takatso e matla ea lithethefatsi. Bohanyetsi ba CRF ba ile ba thibela khetho ea lithethefatsi tse amanang le ts'ebetso e eketsehileng ea ho ikakhela ka setotsoana sa cocaine, nicotine (Koob, 2008), heroin (Greenwell et al a, 2009), le joala (Koob, 2008). Mohlala o makatsang oa litlamorao tsa CRF ho amygdala e holofalitsoeng o ka bonoa mehlaleng ea liphoofolo tsa boitšoaro ba ethanol liphoofolong tseo CRF e ikemetseng ho tsona.1/2 peptide antagonist e kenngoeng amygdala e thibetse keketseho ea boits'oaro ba ethanol nakong ea ho tlohela (Funk et al a, 2006; Koob, 2008).
Le ha e sa ntlafatsoe hantle, bopaki bo fana ka maikutlo a ho kenya letsoho ha lits'ebetso tsa norepinephrine ho amygdala e atolositsoeng seterekeng se seng sa boiketlo le boikemelo bo eketsehang ba boits'oaro bo amanang le ts'episo (Koob, 2009b). E lumellana le karolo ea dynorphin-κ Sistimi ea opioid maemong a hlobaetsang a ho tlosoa hoa lithethefatsi, a κ-Pioid antagonist e thibetse ho nooa ho fetelletseng ho amanang le ho tlosoa hoa ethanol ho likhoto tse itšetlehileng 'me ka mokhoa o ikhethileng o thibetse ts'ebetso ea tekanyo e tsoelang pele ea likhoto ka phihlello e atolositsoeng ea koae (Koob, 2009b; Wee et al a, 2009).
Neuropeptide Y e na le thepa e makatsang e tšoenyang batho ba bang e ts'oeroeng ke amygdala ebile e ts'ellelitsoe hore e be le litlamorao khahlano le CRF maemong a hlohlelletsang a ho tlohela lithethefatsi tsa tlhekefetso (Heilig et al a, 1994; Heilig le Koob, 2007). NPY e fanoe ka intracerebroventricularly e thibelletse ts'ebetso e eketsehileng ea lithethefatsi e amanang le ts'ehetso ea ethanol (Thorsell et al a, 2005a, 2005b). Ho kenella ka NPY ho CeA (Gilpin et al a, 2008) le polelo ea ntlafatso ea vaerase e ntlafalitsoeng ea NPY ho CeA e boetse e thibetse ts'ebetso e eketsehileng ea lithethefatsi e amanang le ts'epahalo ea ethanol (Thorsell et al a, 2007).
Kahoo, keketseho ea CRF ho CeA e etsahalang ka ho tlohella lithethefatsi ka matla ha e na bohlokoa ba bohlokoa feela lithahasellong tse mpe tsa maikutlo le ho khaotsa ho ts'oaroa ke ts'ebeliso e mpe ea lithethefatsi. Ho hula ka matla le hona ho ka eketsa ho lokolloa ha norepinephrine ho BNST le dynorphin ho li-bokellase tsa nucleus, tseo ka bobeli li ka tlatsetsang boemong bo bobe ba maikutlo bo amanang le ho ts'epa. Ts'ebetso e fokotsehileng ea NPY ho CeA le eona e ka kenya letsoho ho tsieleho joalo ka mmuso o amanang le ts'epahalo ea ethanol. Ts'ebetso ea lits'ebetso tsa khatello ea kelello (CRF, norepinephrine, dynorphin), e kopantsoeng le inactivation ea li-system antistress system (NPY) ho amygdala e atolositsoeng e ka etsa hore ho be le khatello e matla ea maikutlo ho tlatselletsang molemong oa ho lemalla. Lisistimi tse ling tse 'maloa tsa neurotransmitter li hlophisitsoe hore li fetole amygdala e atolositsoeng ka bobeli ho tsoa sebakeng sa khatello ea khatello ea kelello (vasopressin, ntho P, orexin) le domain antistress (nociceptin, endocannabinoids; bakeng sa tlhahlobo, bona Koob, 2008). Ts'isinyeho e joalo e kanna ea ba tlatsetso ea bohlokoa mananeong a hanyetsano a pakeng tsa system a thusang ho boloka ts'ebelisano 'me e boetse e rala motheo bakeng sa liphetoho tsa mmuso tse telele ho maikutlo a joalo ka ho ila thipa nako e telele.
Patlisiso mabapi le mekhoa e matlafatsang ea bokhoba ba lithethefatsi tsa batho e se e lekantsoe haholo. Ka mohlala, ka cocaine, amygdala le lateral orbitofrontal cortex li ile tsa bonts'oa hore li hlahisoa ka ts'ebetso e sa lebelloang empa e sa lebelloang ea batho ba sebelisang koae.Kufahl et al a, 2008), empa ho khaotsa koae ho ne ho amana le ho fokotsa haholo ts'ebetsong ea libaka tsa prooption tsa dopamine, ho kenyeletsoa le amygdala (Tomasi et al a, 2007a). Ka lehlakoreng le leng, ho khaotsa ho tsuba ho ne ho amahanngoa le phallo ea mali a khubung ea amygdala, har'a libaka tse ling (Wang et al a, 2007), athe leqhubu la nicotine la nko le fokotsehile phallo ea mali a khubung ea amygdala mme la tlohela batho ba tsubang tloaelo ka tlasa 12h oa ho nyahlatsa (Zubieta et al a, 2001).
Amygdala e kanna ea ba ea hlokahala ka mokhoa o tšoanang bakeng sa ho sebetsana le moputso o motle (Murray, 2007) le tebello ea moputso (Holland le Gallagher, 2004), e ts'oanang le ho sebetsana le moputso o fosahetseng. Haholo-holo e khahlisang molemong oa lipatlisiso tsa likhopolo tsa boko e tla ba ho utloisisa ts'ebetso ea amygdala ho hlahiseng matšoenyeho le maikutlo a seng monate a bonoang khafetsa nakong ea thibelo.
Tlaleho ea morao-rao e bontšitse bohlokoa ba bokhoba ba potoloho ea lipuisano eo ho ka etsahalang hore ebe e amana le amygdala e atolositsoeng le ventral striatum. Phuputso e bonts'itse hore batho ba tsubang ba nang le ts'usumetso ea botlolo ea bona ea bohloka (empa ba sa tsubeng ka liso tse eketsehileng) ba ile ba khona ho khaotsa ho tsuba habonolo mme ntle le ho tsilatsila kapa ba oela hape (Naqvi et al a, 2007). Insula, haholoholo libaka tsa eona tse ka thoko, e hokahana le likarolo tse 'maloa tsa maoto (mohlala, li-cortex tsa ventromedial precental, amygdala, le ventral striatum) mme e bonahala e na le ts'ebetso ea ho nahana, e kopanya tlhahisoleseling ea autonomic le visceral ka maikutlo le ts'usumetso le ho fana ka maikutlo tlhokomeliso ea litlhoko tsena (Naqvi le Bechara, 2009). Ka sebele, lithuto tsa lesapo la bokong li fana ka maikutlo a hore cortex ea ventromedial pre mapemaal cortex le insula ke likarolo tse hlokahalang tsa lipotoloho tse tsamaisitsoeng tse tšehetsang qeto ea maikutlo (Clark et al a, 2008). Tumellanong le khopolo ena, lithuto tse ngata tsa monahano li bonts'a ts'ebetso e kholo mokhoeng oa ho ts'ehetsa nakong ea ho lakatsa (Naqvi le Bechara, 2009). Reactivance ea sebaka sena sa boko e khothalelitsoe hore e sebetse e le sehlahisoa sa biomarker ho thusa ho bolela ho khutla hape.
LITLHAKISO TSA MOLECULAR TSA NEUROPLASTICITY: BINGE / INTOXICATION, LITLHAKISO TSA BOPHELO / LITLHAKISO TSA BOPHELO
Sepheo sa tlhahlobo ea hona joale e holim'a li-neurocircuitry tsa lithethefatsi. Leha ho le joalo, ka ho tšoana le methapo ea methapo ea kutlo ke liphetoho tsa limolek'hule tse etsahalang mehahong ena e le 'ngoe. Ho pepeseha ho sa feleng ho opiates le cocaine ho lebisa ho kengoa ha cyclic adenosine monophosphate Karolo ea Karolo ea Karolo ea (protein) ea protein (CREB) ka har'a nucleus accumbens le CeA (Shaw-Lutchman et al a, 2002; Edwards et al a, 2007). CREB e ka etsoa phosphorylated ke protheine kinase A le protheine kinase e laoloang ke lintlha tsa kholo, e beha sebakeng sa ho kopana bakeng sa mekhoa e mengata ea "intracellular messenger" e ka laolang polelo ea liphatsa tsa lefutso. Ho kenya ts'ebetso ea CREB ka har'a li-nucleus tse bokellanang le lithethefatsi tsa psychostimulant ho hokahane le matšoao a susumetsang a ho tlosoa ha psychostimulant, joalo ka dysphoria, mohlomong ka ho kenella ha opioid peptide dynorphin, e tlamang ho κLi-receptors tsa -opioid 'me li fuoe litlatsetso ho emela mokhoa oa ts'ebetso ea mamello le ts'ehetso (Nestler, 2005). Ts'ebetso e pheta-phetoang ea CREB e phahamisa polelo ea dynorphin ka har'a li-bokellase tsa nucleus, tseo ka lehlakoreng le leng li fokotsehang tšebetso ea dopaminergic, ka bobeli li ka tlatsetsang ho maikutlo a mabe a maikutlo. Extracellular sign-regated kinase ke karolo e 'ngoe ea bohlokoa ea ho saena ho kenella ho nkoa e le karolo ea bohlokoa ho polasetiki e amanang le taolo e pheta-phetoang ea koae, haholo-holo boits'oaro bo botle, moputso oa cocaine, le keketseho e lebelletseng ea ho ts'oara koae ka mor'a ho tlohela (ke hore, ts'ebetso ea ho kenella; Lu et al a, 2006; Li et al a, 2008).
Morero o mong oa limolek'hule bakeng sa taolo ea polasetiki e lebisang bokhobeng ke ho hloka taolo ea phapanyetsano ea cystine-glutamate, e khothalletsoang ho khothaletsa ho ts'oara lipontšo tsa "pathological glutamate" tse amanang le likarolo tse 'maloa tsa potoloho ea bokhoba. Mona, taolo e pheta-pheto ea phapanyetsano ea cocaine blunts cystine-glutamate, e lebisang ho fokotsehileng ha basal le ho eketsa glutamate e hlahisang koae ka har'a li-bokellase tsa "nucleus" tse phehellang bonyane libeke tsa 3 kamora kalafo ea ho qetela ea koae (cocaine) (Baker et al a, 2003). Ntho e qobellang ka ho fetisisa ke ho bona hore kalafo e na le N-acetylcysteine, ka ho etsa hore phapanyetsano ea cystine-glutamate e sirelle, e thibele ho phahama le ho ts'oaroa hoa boitšoaro, e khutlisitse bokhoni ba ho kenya ts'ebetso ea EPP le khatello ea maikutlo ea nako e telele ho li-nucleus tsa li-nucleus, le ho khutlisetsoa ka matla liphoofolong le ho khutlisetsoa maemong a amanang le lithethefatsi ho batho (Moussawi et al a, 2009; LaRowe et al a, 2007; Madayag et al a, 2007).
CREB le man messengersosa a mang a makatsang ba ka kenya tšebetsong lintlha, tse ka fetolang polelo ea gene le ho hlahisa liphetoho tsa nako e telele ho polelo ea protheine, 'me ka lebaka leo, ts'ebetso ea methapo. Leha tsamaiso e matla ea lithethefatsi tsa tlhekefetso e ka baka ts'ebetso e potlakileng (ka nako ea lihora tse) ea litho tsa lelapa la protheine ea Fos, joalo ka c.fos, FosB, Fra-1, le Fra-2 ho li-bokellase tsa nucleus, lintlha tse ling tsa ho ngola, li-isoforms tsa ΔFosB, sebopeho se tsitsitseng sa FosB, li bonts'itsoe ho bokella nako e telele ho feta ea matsatsi (matsatsi) ka taolo e pheta-phetoang ea lithethefatsi (Nestler, 2005). Liphoofolo tse nang le ts'ebeliso ea activFosB li fetellelitse maikutlo a hau liphellong tse khahlisang tsa lithethefatsi tsa tlhekefetso, mme ΔFosB e kanna ea ba 'switch' e tsitsitseng e thusang ho qala le ho boloka boemo ba tahi (McClung et al a, 2004). Hore na (hona joang) lintlha tse joalo tsa mongolo li ama ts'ebetso ea lits'ebetso tsa khatello ea kelello, joalo ka CRF le tse hlalositsoeng ka holimo, li ntse li tlameha ho ikemisoa.
TLHOKOMELISO LE LITLHAKISO
Ka bokhutšoanyane, libaka tse ngata tsa boko le lipotoloho li qhelelletsoa bokhobeng ba lithethefatsi 'me li na le monyetla oa ho kenya letsoho phapang e rarahaneng ea phenotype e bonoang ho batho ba lemaletseng lithethefatsi (Setšoantšo sa 5). Leha tse ling tsa litlolo tsena tse sebetsang li ka ba teng ka tekanyo e kholo kapa e nyane ho lihlopha tsohle tsa lithethefatsi tsa tlhekefetso, tse ling tsa liphetoho li kanna tsa ba tsa mefuta e itseng ea lithethefatsi. Mohlala, ho fokotseha ha nako e telele ho DAT ho striatum ho bonoa ho methamphetamine empa eseng ho joala kapa lithethefatsi tsa koae. Ka lehlakoreng le leng, ho fokotseha ha dopamine D2 li-receptor ka har'a striatum li bonoa lihloohong tse lemaletseng lithethefatsi tsohle tsa tlhekefetso tse fupulitsoeng, le ts'ebetso e eketsehileng ea lits'ebetso tsa khatello ea kelello joalo ka CRF e 'nile ea bonoa mefuteng ea liphoofolo nakong ea ho khaotsa ka matla mefuta eohle ea lithethefatsi. Habohlokoa, ho se tloaelehang ha methapo ea kutlo e hlahang ho motho ea lemaletseng joala le ho ka senoloa ke litšoantšo le / kapa lithuto tsa neuropsychopharmacological ke pontšo ea eseng feela mokhoa o fuoeng oa ho pepeseha lithethefatsi, empa hape le sehlopha sa linaleli se ikhethileng sa lefutso, nts'etsopele le tikoloho. litšobotsi.
LITLHAKISO TSE KHUTLENG
Tswelopele e boletsoeng kaholimo e supa tsela ea lits'ebeliso tsa nako e tlang bakeng sa ho etsa lipatlisiso ka methapo e meng ea methapo ea kutlo ho moralo o le mong oa khopolo ea ho itlopa joala kapa ho tahoa, ho hula / ho ama hampe, le ho nahana ka pele / tebello. Mehlodi e ruileng ea li-neuroscience tsa sejoale-joale tse sebelisitsoeng ho neurobiology ea bokhoba ba tai e fana ka monyetla oa ho se utloisise feela ts'ebetso ea ts'ebetso ea tahi empa e boetse e fana ka linotlolo tsa ho utloisisa tlokotsi le ho fana ka kalafo ea lefu lena le bolaeang.
Boemong ba ho tahoa kapa bokhoba ba potoloho ea bokhoba ba joala, tsela eo neuroplasticity e qalang ka phetoho ea ho thunya mesolimbic dopamine neurons nakong ea tlhahiso ea lithethefatsi ea pele e fetoleloa ho kenella ts'ebetsong ea dorsal striatum, ts'ebetso ea ts'ebetso ea tsamaiso ea methapo, le ho hira litsamaiso tsa khatello ea kelello le. e fella ka drive e matla e setseng ea boitšoaro bo batlang lithethefatsi esita le likhoeli kamora ho khaotsa ho ntse ho tlameha ho ikemisoa. Mohlala, ho na le kamano efe pakeng tsa ho ba kotsing ea ho kenella ntle ho tšusumetso le ho qobelloa ho latela methapo ea methapo ea methapo e hlalositsoeng ka holimo? Lithuto tse joalo tsa nako e tlang li ka kenyelletsa mekhoa ea liphatsa tsa lefutso e tlohang ho ikatiseng ho ea holimo kapa ho hokahaneng ha methapo ea limolek'hule ka har'a potoloho e itseng ea boko e sebelisa theknoloji ea RNA ea hairpin e khutšoane.
Boemong ba ts'usumetso / boiketsetso bo bobe, ho kenella ha methapo ea khatello ea kelello, joalo ka CRF, mehlaleng ea liphoofolo e hloka ho atolosoa ho lits'ebetso tse ling tsa khatello ea kelello le ho hlahlojoa lithutong tsa batho. Mekhoa e meng e mengata ea methapo e amanang le tsamaiso ea khatello ea kelello e se e ntse e hlahlojoa feela, joalo ka dynorphin, NPY, DP, nociceptin le orexin. Hoo e batlang e sa sebetsoe hona joale ke lithuto tsa monahano oa batho tsa karolo ena ea potoloho ea bokhoba ba litekanyetso le monahano oa motho oa lits'ebetso tsa methapo ea kutlo tse amanang le tšusumetso ea ho tlosoa hoa lithethefatsi. Nts'etsopele ea li-ligands tsa radioactive tse fumanehang bakeng sa lithuto tsa monahano oa batho tse tlamang ho li-receptor tsa li-system tsa neurotransmitter tse kaholimo e tla ba tlatsetso e kholo lebaleng.
Boemong ba ho lebella / ba ho lebella, lithuto tsa batho tsa ho hlaseloa li bontša hore preortalal cortex (orbitof Pambal, medial prefrontal, prelimbic / cingulate) le amygdala ea basolateral e bohlokoa litakatsong tsa litheko le litakatso. Hore na litloaelano tse joalo li bonts'a tšitiso ea libaka tsa bongoana tsa kapele le liphetoho mesebetsing ea dopamine, kapa ho seng joalo bontša pherekano ea mantlha ea libaka tse ka pele tse laolang ts'ebetso ea sele ea dopamine, e ntse e lokela ho ikemisoa. Mekhoa e mecha ea ho ithuta ho kopanngoa ha memori e ka thusa ho hlakisa kamano e matla lipakeng tsa moelelo le lithethefatsi. Bohlokoa ba bokhoba ba potoloho ea lipakeng bo kenyelletsang insula le libaka tse ling tse ka bonts'ang khokahano le amygdala e atolositsoeng le ventral striatum. Ho boela u sebetsa ha lipotoloho tsena tsa boko ho ka sebetsa e le sehlahisoa sa biomarker ho thusa ho bolela ho khutla hape le ho thusa ho tseba bokamoso ba kalafo. Lithuto tsa kamora lefu la motho, lithuto tsa laboratori tsa batho, le lithuto tsa methapo ea methapo mohlaleng oa liphoofolo tse tšoanang li ka hlahisa litholoana tse ntle palong ena.
Kamora nako, liphetoho tsa limolek'hule le liphatsa tsa lefutso tse fetisang liphetoho tšebetsong ea methapo methapo eohle e meraro ea potoloho ea bokhoba e hlalositsoeng ka holimo e se e hlakisoa. Liphetoho lits'ebetsong tse laoloang ke li-transmitter, melaoana, esita le tsamaiso ea liphatsa tsa lefutso maemong a epigenetic li ka hlalosa hore na lipotoloho li ajoa joang, ho lula li sa sebetse hantle le ho fana ka tlokotsi ho taolo qalong kapa nako e telele ea ho thibeloa. Qetellong, sepheo sa ts'ebetso ea methapo ea kutlo se hlahisitsoeng ka moralo oa ts'ebetso ea methapo ea kutlo e tla fana ka lipheo tsa ho tseba ho ba kotsing ea liphatsa tsa lefutso ho palo ea batho, mme ho ba kotsing ea liphatsa tsa lefutso lithutong tsa motho ho ka supa liphofu tse ncha tse lokelang ho hlahlojoa maemong a boithuto ba liphoofolo.
lumela hore baa fokola
Ena ke nomoro ea phatlalatso 20084 e tsoang ho TheHTMLps Research Institute. Litokisetso tsa mosebetsi ona li tšehelitsoe ke Setsi sa Pearson sa Alcoholism le Tlhatlhobo ea Bokhoba le Litsi tsa Naha tsa lithuso tsa bophelo bo botle AA12602, AA08459, le AA06420 ho tsoa Setsing sa Naha sa Ts'ebeliso e Mpe ea Joala; DA04043, DA04398, le DA10072 ho tsoa Setsing sa Naha sa Ts'ebeliso e Mpe ea Lithethefatsi; DK26741 ho tsoa Setsing sa Naha sa Lefu la Ts'oaetso ea Lefu la Ts'oa Le Lefu la Ts'oaetso le Mafu; le 17RT-0095 ho tsoa ho Lenaneo la Lipatlisiso le amanang le lefu la koae ho tsoa Naheng ea California. Re leboha Michael Arends le Ruben Baler ka thuso ea bona mabapi le ho hlophisa pampiri.
Mongolo o botlaaseng ba leqephe
QETHA
Bangoli ba phatlalatsa hore ha ho lintoa tse thahasellisang.
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