Terry E Robinson * le Kent C Berridge
Philos Trans R Soc Lond B Biol Sci. 2008 Mphalane 12; 363 (1507): 3137–3146.
E phatlalalitsoe marang-rang 2008 July 18. Doi: 10.1098 / rstb.2008.0093.
Thuto e Felletseng - Khopolo ea khothatso ea ho lemalla bokhoba: tse ling tsa litaba tsa morao-rao
Copyright © 2008 Mokhatlo oa Royal
Lefapha la Psychology (Lenaneo la Biopsychology), Univesithi ea Michigan, Hall ea Bochabela, 530 Church Street, Ann Arbor, MI 48109, USA
* Sengoli le aterese bakeng sa ngollano: Lenaneo la Biopsychology, Lefapha la Psychology, Univesithi ea Michigan, East Hall, 525 East University Avenue, Ann Arbor, MI 48109-1109, USA (Email: [imeile e sirelelitsoe]
HO HLOKA
Re hlahisa kakaretso e khuts'oane ea mohopolo oa tšusumetso ea ts'usumetso ea ho lemalla. Sena se fana ka maikutlo a hore bokhoba bo bakoa haholo ke maikutlo a susumetsoang ke lithethefatsi bokong ba mesocorticolimbic system bo hlahisang tšusumetso e bang teng ho susumetseng ho amanang le moputso. Haeba e fanoa ka hypersensitive, lits'ebetso tsena li baka tšusumetso ea methapo ea kutlo ('ho batla') lithethefatsi. Re araba lipotso tse ling tsa hajoale ho kenyelletsa: karolo ea ho ithuta ho hohelang maikutlo le tšusumetso ea motho ke eng? Na maikutlo a khothalletsang takatso a hlaha litlamong tsa batho? Na nts'etsopele ea boits'oaro bo ts'oanang le bokhoba ba liphoofolo ho amanang le maikutlo a ho hlasimoloha? Mokhoa o motle ka ho fetisisa oa ho bapisa matšoao a bokhoba ba ho lemalla, o sebelisa mefuta ea liphoofolo ke ofe? Mme, qetellong, likarolo tsa boithabiso tse tlatselletsang kapa ho itlhahisa e le joala ke eng?
Mantsoe a bohlokoa: sensitization, dopamine, litloaelo, koae, amphetamine, tšusumetso
1. SELELEKELA
Ka nako e 'ngoe bophelong ba bona, batho ba bangata ba leka sethethefatsi se ka lemalloang (mohlala, joala). Leha ho le joalo, ke ba fokolang ba lemalloang. Bokhoba bo fana ka maikutlo a ho batla lithethefatsi le boits'oaro ba ho batla lithethefatsi, tse nkang nako le menahano ea motho ka mokhoa o fetelletseng, mme li ntse li tsoela pele leha ho bile le litlamorao tse mpe (Hasin et al. 2006). Ba lemaletseng lithethefatsi le bona ba thatafalloa ho fokotsa kapa ho emisa ts'ebeliso ea lithethefatsi, leha ba lakatsa ho etsa joalo. Kamora nako, ba lemaletseng lithethefatsi ba kotsing ea ho khutlela mokhoeng leha ba se ba qetile nako e telele ba se ba sa o tlohele hape le kamora hore matšoao a ho ikhula a nyamele. Kahoo, potso ea bohlokoa lipatlisisong tsa bokhoba ba tahi ke hore: ke eng e ikarabellang bakeng sa phetoho ea bokhoba ba batho ba fokolang ba kotsing?
Lilemong tse 20 tse fetileng ho bile le kananelo e ntseng e eketseha ea hore lithethefatsi li fetola bokooa ba batho ba lemaletseng litsela tse rarahaneng le tse phehellang, li phehella hoo li fetisang liphetoho tse ling tse amanang le mamello le ho khaotsa. Ho bohlokoa ho khetholla liphetoho tsa boko tse bakang phetoho ea ho lemalla tšebeliso e mpe ea lithethefatsi kapa boithabiso, le likarolo tse etsang hore batho ba itseng ba amehe haholo ke phetoho (Robinson & Berridge 1993; Nestler 2001; Hyman et al. 2006; Kalivas & O'Brien 2008). Liphetoho tse tsoelang pele tse tlisoang ke lithethefatsi bokong li fetola lits'ebetso tse ngata tsa kelello, li baka matšoao a fapaneng a bokhoba. Re khothalelitse khopolo ea ts'usumetso ea bokhoba ba tahi, e phatlalalitsoeng ka lekhetlo la pele ho 1993, hore phetoho ea bohlokoahali ea liphetoho tsena tsa kelello ke 'sensitization' kapa hypersensitivity ho litlamorao tsa ts'usumetso ea lithethefatsi le litlamorao tse amanang le lithethefatsi (Robinson & Berridge 1993). Ts'usumetso ea ts'usumetso e hlahisa leeme la tlhokomelo e lebisang tlhokomelong e amanang le lithethefatsi le tšusumetso ea mafu bakeng sa lithethefatsi ('ho batla' ho qobelloang). Ha e kopantsoe le taolo e holofetseng ea taolo ea boits'oaro, khothatso ea khothatso e fella ka matšoao a mantlha a bokhoba (Robinson & Berridge 1993, 2000, 2003). Khothatso ea ts'usumetso e hohetse thahasello e kholo lilemong tse 15 tse fetileng mme ka hona, re bone ho le bohlokoa ho ntlafatsa pono ea rona. Re hlahisa mona kakaretso e khuts'oane ea idiosyncratic ea pono ena ea tahi le ho hlahisa lintlha tsa morao-rao.
2. TLHALOSO EA SEBETE EA TLHALOSO KE EFE LE TLHALOSO EA HO ITHUTA?
Khopolo-taba ea mantlha ea khopolo ea ho khothaletsa bokhoba ba tahi (Robinson & Berridge 1993) ke hore ho pepeseha khafetsa ho lithethefatsi tse ka lemalloang, ho batho ba nang le ts'oaetso le maemong a itseng, ho ka lula ho fetola lisele tsa boko le lipotoloho tse atisang ho laola tšusumetso ea tšusumetso e matla ea tšusumetso ho ba bang. , ts'ebetso ea kelello e amehang boitšoarong bo susumetsoang. Sebopeho sa 'li-neuroadaptations' tsena ke ho fa lipotoloho tsena tsa boko hypersensitive ('sensitized') ka tsela e lebisang maemong a tšoaetsanoang a ts'usumetso e bakoang ke lithethefatsi le litlamorao tse amanang le lithethefatsi.
Ho phehella ha maikutlo a ho susumetsa ho etsa hore tšusumetso ea methapo ea kutlo (ho batla) bakeng sa lithethefatsi e tšoarelle lilemo, le kamora ho khaotsa ts'ebeliso ea lithethefatsi. Senceitised incentiveence salience e ka bonahatsoa ka boits'oaro ka ho ikemisetsa (joalo ka ho batla ho sa tsebeng letho) kapa lits'ebetso tse hlakileng (joalo ka tse lakatsang), ho latela maemo. Qetellong, ho tsepamisa maikutlo lithethefatsing haholo ho bokhoba ba lithethefatsi ho hlahisoa ke tšebelisano lipakeng tsa ts'usumetso ea mekhoa ea ho sebelisa litšusumetso le mekhoa ea ho ithuta eo hangata e tataisang sepheo ho lipheo tse tobileng le tse nepahetseng.
Ho ithuta ho hlakisa sepheo sa takatso, empa ho bohlokoa ho hlokomela hore ho ithuta ka bonngoe ha hoa lekana bakeng sa tšusumetso ea mafu ho noa lithethefatsi. Kahoo, re pheha khang ea hore ts'usumetso ea mafu e bakoa ke ho hlohlelletsa lipotoloho tsa boko tse lumellanang le lits'ebetso tsa khothatso ea Pavlovian (ke hore khothatso ea khothatso). Leha ho le joalo, ho bohlokoa ho totobatsa hore lits'ebetso tsa boithuto tse kopaneng li ka hlophisa polelo ea ts'usumetso ea methapo libakeng tse itseng kapa linako (eseng tse ling), hape le ho tataisa tataiso ea litlhahiso tsa khothatso. Ke ka hona ho hlohlelletsa boits'oaro hangata ho hlahisoang feela maemong ao litlhare li kileng tsa ba ho ona (Stewart & Vezina 1991; Anagnostaras & Robinson 1996; Robinson et al. 1998), mme e ka bonts'a ts'ebetso ea mofuta oa 'maemo a ho beha' ea mochini (Anagnostaras et al. 2002). Ho ithuta ho kanna ha talingoa e le moalo holim'a methati ea mantlha ea ho matlafatsa batho ka mokhoa o tlase, joalo ka ha thuto e laola taolo ea ts'ebeliso ea lits'ebetso tse sa amaneng le khatello ea maikutlo le bohloko. Taolo ea maemo mabapi le polelo ea ho hlohlelletsa e fana ka sesebelisoa se seng se ikarabellang hore na hobaneng lithethefatsi li 'batla' haholoholo ha li le maemong a amanang le lithethefatsi.
Kamora nako, ka ho hasanya ho feta mohopolo o kopaneng oa ho batla liphofu tsa lithethefatsi, khothatso ea ts'usumetso le eona ka linako tse ling e ka tšolohela liphoofolong kapa bathong ho isa lipheo tse ling, joalo ka lijo, thobalano, papali ea chelete, jj. (Mitchell & Stewart 1990; Fiorino & Phillips 1999a, b; Taylor le Horger 1999; Nocjar & Panksepp 2002). Mohlala, kalafo e nang le meriana ea dopaminergic bathong ba bang ba bakuli e ka lebisa ho 'dopamine dysregulation syndrome' (DDS) e sa bonahaleng feela ka tšebeliso e mpe ea lithethefatsi empa hape ka linako tse ling ka 'papali ea papali ea chelete, bosodoma, ho itlopa lijo ... le punding, mofuta ea boitšoaro bo rarahaneng ba boitšoaro '(Evans et al. 2006, leq. 852).
(a) Ho khothatsa maikutlo: ho feta feela ho ithuta
E se e le ntho e tsebahalang ho bitsa bokhoba e le 'ho ithuta ho ithuta' (Hyman 2005), empa re nahana hore poleloana ena e kanna ea fokola haholo hore e ka lekana le nnete. Ho ithuta ke karolo e le 'ngoe feela ea ts'ebetso mme mohlomong ha se eona e tlatsetsang haholo ho phehelleng ha lithethefatsi.
Mofuta o nang le tšusumetso e kholo ea 'thuto ea maikutlo' o fana ka maikutlo a hore lithethefatsi li khothaletsa ho ithuta ka litloaelo tse matla tsa 'automatized' stimulus-reaction (S-R), mme ho nahanoa hore ka tlhaho ea bona mekhoa ea S-R e fana ka khatello ea boitšoaro (Tiffany 1990 ; Berke & Hyman 2000; Everitt et al. 2001; Hyman et al. 2006). Leha ho le joalo, ho thata ho nahana hore na tšusumetso efe kapa efe ea lithethefatsi ts'ebetsong ea ho ithuta feela e ka fana ka khatello ea boitšoaro, ntle le haeba karolo e 'ngoe ea tšusumetso e ne e ameha, mme litloaelo tsa S-R ha li hlophisoe ke mabaka a susumetsang (Robinson & Berridge 2003) . Na litloaelo tsa S-R tse iketsang li fetoha ntho e qobelloang feela ka lebaka la ho ithuta hantle haholo? Re na le lipelaelo. Mekhoa e matla ea S-R ha e hlile e lebisa ho boitšoaro bo qobelloang: mesebetsi e joalo ka ho tlama lieta, ho hlatsoa meno, jj. Mekhoa e meng ea ts'usumetso e bonahala e hlokahala ho hlalosa hore na hobaneng motho ea lemaletseng ho tsoha hoseng a sena sethethefatsi a qeta letsatsi a le lethathamong la boits'oaro bo thata le ka linako tse ling, joalo ka bomenemene, bosholu le lipuisano, kaofela li bonahala li susumetsoa ho fumana lithethefatsi. Ba lemaletseng lithethefatsi ba etsa seo ba tlamehang ho se etsa le ho ea moo ba tlamehang ho ea fumana lithethefatsi, leha ho ka hlokahala liketso le litsela tse e-so ka li etsoa pele. Boitšoaro bo joalo bo tsepameng empa bo feto-fetohang bokhobeng bo bontša tšusumetso ea mafu bakeng sa lithethefatsi tse ke keng tsa hlalosoa ka ho tsosa litloaelo tsa SR. Ka 'nete, khopolo e thata ea tloaelo ea S-R e ka hloka hore motho ea lemaletseng joala, ha a tsoha hoseng a se na sethethefatsi, hore a iketsetse' ka mokhoa o iketsang 'ka tatellano e tšoanang ea khale ea liketso tseo ba neng ba tloaetse ho li sebelisa ho fumana lithethefatsi, ekaba liketso li ne li le joalo e sebetsang hona joale kapa che. Leha ho le joalo ba lemalloang lefatšeng la 'nete ha se li-automatone tsa S-R; ba na le tsebo e ngata, haeba ho se letho le leng.
Ka lehlakoreng le leng, motho e mong le e mong o tlameha ho lumela hore litloaelo tsa S-R mohlomong li kenya letsoho ho boits'oaro le litloaelo tse amanang le tšebeliso ea lithethefatsi ha li se li fumanoe (Tiffany 1990), mme ho bonts'itsoe hore kalafo ka lithethefatsi e thusa nts'etsopele ea litloaelo tsa S-R ho liphoofolo (Miles et al. 2003; Nelson & Killcross 2006), mohlomong ka ho hira ea dorsal striatum (Everitt et al. 2001; Porrino et al. 2007). Re boetse re hlokomela hore litloaelo li kanna tsa hlahella haholo litekong tse tloaelehileng tsa ho itaola ha liphoofolo, moo ho nang le karabelo e le 'ngoe feela e ka etsoang (mohlala, tobetsa lever) makhetlo a likete tikolohong e futsanehileng haholo ho fumana liente tsa lithethefatsi. Kahoo, re nahana hore lithuto tsa hore na lithethefatsi li khothaletsa ho ithuta ha litloaelo tsa S-R li tla fana ka leseli la bohlokoa mabapi le taolo ea boits'oaro ba ts'ebeliso ea lithethefatsi ho batho ba lemaletseng lithethefatsi, empa ena ha se bothata bo ka sehloohong ba bokhoba ba tahi.
(b) Kameho ea tšusumetso ea maikutlo le ts'usumetso ea kelello
Khopolo ea khothatso ea ts'usumetso e shebane le liphetoho tse susumetsoang ke tšusumetso molemong oa tšusumetso ea ts'ebetso le liphetoho tse amanang bokong, empa re amohetse hore liphetoho tse ling tsa boko li tlatsetsa hampe ho lemalleng, ho kenyelletsa le ts'enyo kapa ho se sebetse hantle mokhoeng oa kotlo o thehang khetho ea kelello le ho etsa liqeto ( Robinson & Berridge 2000, 2003). Liphuputso tse ngata li bontšitse hore liphetoho ho 'mesebetsi ea bolaoli', ho kenyelletsa hore na liphetho tse ling li hlahlojoa joang le liqeto le likhetho tse etsoang, li etsahala ho ba lemalloang le liphoofolong tse fuoeng lithethefatsi (Jentsch & Taylor 1999; Rogers & Robbins 2001; Bechara et al. 2002; Schoenbaum & Shaham 2008). Re lumela hore bofokoli ba taolo ea phethahatso bo bapala karolo ea bohlokoa ho etseng liqeto tse fosahetseng ka lithethefatsi, haholo ha li kopantsoe le tšusumetso ea mafu a bakoang ke ts'usumetso ea ts'usumetso.
3. TLHOKOMELISO KE ENG?
Ho bonolo ho fumana maikutlo ho tsoa lingoliloeng hore boits'oaro ba boits'oaro bo kanna ba lekana le 'ho matlafatsa tšebetso ea batho ba tsamaeang ka maoto', empa ho hula hlooho ke e 'ngoe feela ea litlamorao tse fapaneng tsa kelello le lithethefatsi tse mamelloang, tseo bongata ba tsona li sa arohaneng (Robinson & Becker 1986 ). Ho bohlokoa ho hopola hore moelelong ona lentsoe sensitization le bolela feela keketseho ea litlamorao tsa lithethefatsi tse bakoang ke tsamaiso ea lithethefatsi e phetoang. Ntho ea bohlokoa bakeng sa khopolo ea khothatso ea khothatso ha se 'locomotor sensitization', kapa 'psychomotor sensitization', empa ke khothatso ea khothatso. Ntle le ts'ebetso ea psychomotor ho nahanoa hore e bonts'a tšebetso ea litsamaiso tsa tšusumetso ea boko, ho kenyeletsoa le mesotelencephalic dopamine system (Wise & Bozarth 1987), sensitization ea psychomotor e kanna ea sebelisoa joalo ka bopaki (leha e le bopaki bo sa tobang) bakeng sa hypersensitivity ho potoloho e susumetsang e nepahetseng. Empa ke hypersensitivity ho potoloho ena e susumetsang, eseng li-locomotion circry, tse tlatsetsang haholo ho batleng lithethefatsi tsa lithethefatsi.
(a) Bopaki bo tobileng bakeng sa tlhotlheletso ea maikutlo
Ho na le bopaki bofe bakeng sa khopolo ee ea bohlokoa ea tšusumetso ea maikutlo a ts'ebeliso ea lithethefatsi e sa khaotseng e utloisang likarolo tse tlase tsa neural tse ikarabellang bakeng sa tšusumetso ea ho hlohlelletsoa ho susumetsa ho amanang le moputso? Taba ea pele, ho pepesetsoa lithethefatsi tse ngata tsa tlhekefetso ho ntlafatsa litlamorao tsa lithethefatsi tse lekantsoeng tse sebelisang mefuta e fapaneng ea boitšoaro. Ka tsela eo sensitization e nolofalletsa ho fumaneha ha morao-rao ha boits'oaro ba taolo ea lithethefatsi, lithahasello tse hlophisitsoeng bakeng sa libaka tse enngoeng ka lithethefatsi le tšusumetso ea ho sebeletsa lithethefatsi joalo ka ha ho bonts'itsoe ke 'break break' lenaneong le ntseng le tsoela pele la ratio (Lett 1989; Vezina 2004; Ward et al. 2006).
Bopaki bo ikhethileng bakeng sa ts'usumetso ea ts'usumetso bo tsoa liphuputsong tse etselitsoeng ho lekola ka kotloloho liphetoho tse bakiloeng ke lithethefatsi molemong oa tšusumetso o bakoang ke tšusumetso e amanang le moputso, le ho qhelela ka thoko litlhaloso tse ling tsa keketseho ea boits'oaro bo laoloang ke moputso ho latela thuto ea tloaelo, jj. thepa ea khothatso ka ho kopanngoa le moputso, 'me' li-conditioned stimuli '(CS) tse matlafalitsoeng ke bohloeki li na le litšobotsi tse tharo tsa mantlha (Berridge 2001; Cardinal et al. 2002). (i) Ba ka etsa hore batho ba atamele ho bona (ba be ba 'batloe'), ba sebetse e le 'limakete tse susumetsang' (tse ka lekanngoang ke boits'oaro ba boemo bo hlophisitsoeng ba Pavlovia kapa 'ho latela lets'oao'). (ii) Ba ka matlafatsa liketso tse tsoelang pele ka ho hlohlelletsa maikutlo a ho batla meputso ea bona e sa amaneng le maemo (e ka lekanngoang ke phetisetso ea seletsa sa Pavlovian). (iii) Ba ka sebetsa joalo ka batšehetsi ka bobona, ba matlafatsa ho fumanoa ha karabelo e ncha ea seletsa (e ka lekanngoang ke matlafatso a maemong). Kahoo, bopaki bo totobetseng ka ho fetesisa ba khothatso ea ts'usumetso bo tsoa liphuputsong tse bonts'ang hore kalafo ea nako e fetileng ea lithethefatsi, e hlahisang sensitization ea psychomotor, e thusa likarolo tsohle tse tharo tsa ts'usumetso e matlafatsang: Boits'oaro ba Pavlovia boits'oaro (Harmer & Phillips 1998); Phetiso ea lisebelisoa tsa Pavlovian (Wyvell & Berridge 2001); le maemo a matlafatso (Taylor & Horger 1999; Di Ciano 2007).
Re lokela ho amohela, leha ho le joalo, hore liphuputsong tse ngata mabapi le tšusumetso ea maikutlo a khothalletsang moputso ka tlhaho (hangata lijo kapa metsi), eseng moputso oa lithethefatsi, e ne e sebelisetsoa ho fa CS thepa e khothalletsang thepa. Ho thata ho araba potso ea hore na maikutlo a pele ho mona a ka thusa ka kotloloho menyetla ea tšusumetso e amanang le lithethefatsi litekong tsa liphoofolo hobane ho tsamaisoa ha khothatso ka taolo ea lithethefatsi ka bo eona ho ka hlahisa maikutlo. Ebile, ho tlalehiloe haufinyane haholo hore lefapha la thekiso ea lithethefatsi ka mokhoa oa Pavlovian (ke hore, ntle le ketso e fe kapa e fe) le ka iphumanela mokhoa ona (Uslaner et al. 2006). Ho bohlokoa, ka hona, hore lipatlisisong tsa morao-rao Di Ciano (2007) li fumane hore sensitization ea cocaine e nolofalitse maemo a matlafatsang a matlafatso a amanang le koae, a tsamaellanang le maikutlo a susumetsang. Ehlile, taba ea hore bakuli ba nang le DDS pathologically ba batla lithethefatsi e boetse e lumellana le mohopolo oa tšusumetso ea maikutlo (Evans et al. 2006). Leha ho le joalo, sena ke sebaka se lokelang ho etsoa lipatlisiso tse ngata.
Mokhoa o mong oa ho atamela hore na ts'usumetso ea ts'usumetso e ea etsahala ke ho botsa potso ka pono ea boko. Ka mantsoe a mang, na ho matlafatsa ho eketsa ts'ebetso ea methapo ea methapo ea methapo ea kutlo e khothalletsang boleng ba tšusumetso ea tšusumetso ea moputso? Liphuputso tse 'maloa li bonts'a hore ho joalo (Tindell et al. 2005; Boileau et al. 2006; Evans et al. 2006). Mohlala, ho matlafatsa amphetamine ho likhoto ho eketsa mekhoa e khethehileng ea ho thunya li-neuron mehahong ea mesolimbic e khothalletsang botsitso ba moputso oa CS (Tindell et al. 2005). Ho batho, kalafo e phetoang ea amphetamine e tlalehiloe e le ho matlafatsa amphetamine-e hlohlelletsa dopamine 'ho lokolloa' ho ventral striatum, esita le selemo kamora kalafo ea ho qetela ea lithethefatsi (Boileau et al. 2006), le ts'ehetso ea tokollo ea dopamine le eona e tlalehiloe ho bakuli le DDS (Evans et al. 2006). Qetellong, leha re sa tsebe hantle hore na ke liphetoho life tse ngata bokong tse hlahisoang ke lithethefatsi tse bakang phetoho ea kelello ea khothatso, re fana ka maikutlo a hore bopaki bo fanoeng kaholimo bo bontša hore ho pepeseha ha lithethefatsi khafetsa ho fetola boitšoaro bo nepahetseng, kelello lits'ebetso le likarolo tsa boko ka botsona ka tsela e boletsoeng esale pele ke bopaki ba prima facie bakeng sa sengoloa.
4.A BOTSOALLE BA QETELA HO BATHO?
Teko e 'ngoe eo re utloileng khafetsa ka eona ea maikutlo a khothalletsang maikutlo lilemong tse leshome tsa pele e ne e le hore ho ne ho se na bopaki ba hore batho ba bonts'a boitšoaro kapa maikutlo a neural. Leha ho le joalo, lilemong tse 'maloa tse fetileng, liphuputso tse' maloa joale li bontšitse maikutlo le mekhoa ea maikutlo ho batho (re lebisa babali tlhahlobo e nahannoeng ea sehlooho ke Leyton 2007). Ho joalo, le pejana ho ile ha hlokomeloa hore batho ba bonts'itse maikutlo a amanang le paranoia e amanang le paranoia le stereotypy-indcing ('punding') ea lithethefatsi tsa psychostimulant, leha ho le joalo bohlokoa ba sena ho ts'usumetsong ea ts'usumetso e ne e sa tsejoe hohle. Hoa thahasellisa hore ebe ho hlahisitsoe mochini o khothalletsang litšusumetso tsa mofuta oa tšusumetso ho khothaletsa matšoao a lefu la kelello le "psychoses" (Kapur et al. 2005).
Ka bokhutšoanyane, mabapi le bopaki ho batho bakeng sa ts'usumetso ea ts'usumetso, taolo e pheta-phetoang ea amphetamine ho batho e ka hlahisa ts'ehetso e sa khaotseng ea boits'oaro (mohlala, likarabo tsa mahlo, matla le matla a matla), haholo-holo litekanyetsong tse phahameng (Strakowski et al. 1996; Strakowski & Sax 1998; Boileau et al. 2006). Hape, ho batho ba lemaletseng lithethefatsi, tlhokomelo e sekametse mekhoeng e bonts'ang e amanang le lithethefatsi maemong a hanghang le a sa hlakang, joalo ka ha e lekantsoe ka ho latela mahlo, joalo ka ha eka litlhare tsa lithethefatsi li ne li hohela ebile li hohela tlhokomelo ka tsela e lumellanang le ts'usumetso ea khothatso (Wiers & Stacy 2006). Bopaki ba Neural ba sensitization le bona bo hlalositsoe haufinyane ho batho, joalo ka ha ho boletsoe kaholimo. Tsamaiso e pheta-phetoang ea amphetamine e baka ts'ehetso ea ho lokolloa ha dopamine bathong, leha qholotso ea lithethefatsi e fanoa selemo hamorao (Boileau et al. 2006), le litlhahiso tsa lithethefatsi le tsona li baka karabelo e matla ea dopamine mehahong e tšoanang e amanang le moputso (Boileau et al. 2007; bona le Childress et al. 2008). Ho khahlisang, karabelo e ts'oanang ea sensitized dopamine ho l-DOPA e etsahala ho bakuli ba Parkinson ba nang le seo ho thoeng ke DDS (Evans et al. 2006). Ho bakuli bana, l-DOPA e baka maemo a phahameng ka mokhoa o sa tloaelehang oa ho lokolloa ha dopamine ka har'a ventral striatum joalokaha eka e matlafalitsoe. Ka boits'oaro, bakuli ba nang le DDS ba qobella lithethefatsi tsa dopaminergic maemong a feteletseng, mme ba bonts'a mesebetsi e meng e qobelloang, ho kenyelletsa papali ea chelete le punding (mofuta o rarahaneng oa boits'oaro ba boitšoaro). Mohlomong ho khahlisang ka ho fetesisa ke hore tokollo ea dopamine e eketsehileng e amahanngoa le litekanyetso tse eketsehileng tsa ho batla lithethefatsi empa e se 'ho li rata' ho bakuli ba noang lithethefatsi tsa bona tse ngata haholo (Evans et al. 2006). Liphetho tsena kaofela li tsamaellana le khothatso ea ts'usumetso, mme ho thata ho li hlalosa ka maikutlo a mang a bokhoba.
Leha ho le joalo, ho tlameha ho ananeloa hore lingoliloeng tsa hajoale li na le liphetho tse hananang mabapi le liphetoho tsa boko ba dopamine ho ba lemalloang. Mohlala, ho tlalehiloe hore batho ba lemaletseng koae e tlositsoeng ke chefo ba hlile ba bontša phokotso ea tokollo ea dopamine ho fapana le keketseho e matlafalitsoeng e hlalositsoeng kaholimo (Volkow et al. 1997; Martinez et al. 2007). Leha ho le joalo, litlaleho tsena li hloka ho hlalosoa ka hloko, hobane mefuta e mengata e sebelisana ka litsela tse rarahaneng ho tseba hore na ts'ehetso e hlahisoa sebakeng kapa nako efe kapa efe. Haholo-holo, joalo ka ha ho hlalositsoe ke Leyton (2007), karolo ea moelelo ke ea bohlokoa ho faneng ka polelo ea ho hlohlelletsa ka kakaretso, ka hona ho eketsa keketseho ea tokollo ea dopamine. Boithuto ba liphoofolo bo bonts'itse hore polelo ea ho hlohlelletsa e fetotsoe ka matla ke maemo ao lithethefatsi li fuoang ho ona (Robinson et al. 1998), mme batho ba kanna ba ameha le ho feta maemong a kelello (Leyton 2007). Mohlala, ho matlafatsa le ho ntlafatsa tokollo ea dopamine hangata ha e bonahale haeba liphoofolo li lekoa maemong ao lithethefatsi li so kang li ba le ona (Fontana et al. 1993; Anagnostaras & Robinson 1996; Duvauchelle et al. 2000). Ka hona, ho ipapisitsoe le lingoliloeng tsa liphoofolo, batho ba lemaletseng lithethefatsi ha baa lokela ho lebelloa ho bonts'a ts'ehetso ea boits'oaro kapa ho matlafatsa tokollo ea dopamine haeba tikoloho eo ba fuoang 'phephetso' ea lithethefatsi (mohlala. Scanner) e fapane haholo le maemo ao lithethefatsi li nkuoeng ho ona pele ho. Hoa hlokomeleha hore pontšong e ntlehali ho fihlela hajoale ea sensitized dopamine release bathong, bafuputsi ba ile ba hlokomela ho boloka maemo a ts'oanang ka ho fana ka ts'ehetso ea kalafo ea lithethefatsi maemong a tšoanang a ileng a sebelisoa hamorao ho etsa liteko (scanner; Boileau et al. 2006). Kahoo, lithutong tsa nako e tlang, moelelo o hloka ho tsotelloa pele ho nahanoa hore se bonoang maemong a laboratori se bonts'a se etsahalang ha ba lemalloang ba noa lithethefatsi maemong a bona a tloaelehileng. Kamora nako, ho bohlokoa hape hore re se leke ts'ehetso kapele kamora ho emisa ts'ebeliso ea lithethefatsi empa re emele ho fihlela mamello e kokobetse, hobane mamello e ka pata polelo ea ts'ehetso, le hobane ts'ehetso e hlahisoa hantle kamora nako ea 'poloko '(Robinson & Becker 1986; Dalia et al. 1998).
Ntho e 'ngoe e fumanoeng ho batho e shebahalang e sa lumellane le maikutlo a ho hlaka ke hore batho ba lemaletseng koae ba tlalehoa ba e-na le litekanyetso tse tlase tsa li-dopamine D2 receptors le kamora ho qeta nako e telele (Volkow et al. 1990; Martinez et al. 2004). Sena se supa boemo ba hypodopaminergic ho fapana le boemo ba maikutlo (Volkow et al. 2004). Leha ho le joalo, hape, ho na le mabaka a ho ba hlokolosi. Taba ea pele, kalafo ea psychostimulant ho litoeba, ho kenyelletsa le taolo ea koae, e baka boitšoaro bo botle ho li-agonist tsa D2, joalokaha eka D2 receptors e eketsehile kapa e tebile haholoanyane (Ujike et al. 1990; De Vries et al. 2002; Edward et al. 2007). Lebaka la phapang ena ha le hlake, empa qeto e le 'ngoe e ka hlahisoang ke ho nka hore li-receptor tsa Dopamine D2 li ka ba teng ho e' ngoe ea linaha tse peli tse kopaneng: naha e amanang le maemo a phahameng le e amanang le maemo a tlase, 'me dopamine e fana ka litlamorao tsa eona tse sebetsang. ka ketso ho li-receptors feela (Seman et al. 2005). Mekhoa e mengata ea phekolo e hlahisang supatensitivity ea D2 e boetse e baka keketseho ea li-receptor tsa striatal ka likhoto, empa u se ke oa fetoha kapa hona ho fokotsa kakaretso ea D2 binding (Seman et al. 2005). Habohlokoa ka ho fetisisa bakeng sa lipuisano mona, boiphihlelo ba ho ithekisa ka koae (Briand et al. 2008) le sensitization ho amphetamine (Seman et al. 2002, 2007) le tsona ho tlalehiloe hore li hlahisa keketseho e phehellang ea palo ea li-receptor tsa striatal, ntle le phetoho ka ho tlamaha ha D2 ka kakaretso (ka hona mohlomong ho fokotseha ho lekanang ha li-receptors). Ligands tse sebelisitsoeng ho fihlela joale bakeng sa lithuto tsa li-vopamine D2 receptors ho batho ha li khetholle pakeng tsa linaha tse tlase le tse phahameng tsa tumellano ea D2 receptor, ka hona li ka lahleheloa ke liphetoho tse tobileng ho li-receptors, 'me tsa fana ka maikutlo a fosahetseng mabapi le ts'ebetso ea dopamine. (Seeman et al. 2005). Kahoo, ho tla ba bohlokoa ho etsa lithuto ka li-ligands tse ka hlalosang li-receptor ka ho khetheha bathong pele ho fihlela qeto ea hore lithethefatsi li eketsehile kapa li fokolitse ho saena hoa D2.
5. NA ETSA LITLHAKISO TSA 'NETE-PELE TSA' MAMELLO JOALOKA LITLHAKISO TSA BOPHELO?
Boholo ba lithuto tsa liphoofolo tsa lithethefatsi tse lemalloang li sebelisitse mekhoa le mekhoa e sa amaneng le bokhoba ba motho. Mohlala, bopaki joale bo bontša hore phihlello e fokolang ea lithethefatsi tse itlhommeng pele ha e sebetse ho hlahisa matšoao a tahi liphoofolong joalo ka ho fana ka phihlello e pharalletseng, ekaba ka ho lelefatsa palo ea matsatsi ao liphoofolo li lumelloang ho iketsetsa lithethefatsi (Wolffgramm & Heyne 1995; Heyne & Wolffgramm 1998; Deroche-Gamonet et al. 2004), kapa ka ho eketsa ho fihlela lihora tse 'maloa nako ea lithethefatsi e teng letsatsi ka leng (Ahmed & Koob 1998). Phuputsong e 'ngoe, ho nkile likhoeli tse' maloa ho itšireletsa ka methapo (IV) pele likhoto tse ling li qala ho ba le matšoao a kang a ho lemalla lithethefatsi (Deroche-Gamonet et al. 2004), ho kenyeletsoa le ts'ebetso e tsoelang pele ea ho batla lithethefatsi nakong ea kotlo kapa ha lithethefatsi li le teng. tse tsejoang hore ha li fumanehe, lebaka le matla la ho fumana lithethefatsi, le boits'oaro bo matla ba ho 'khutlela morao' kamora ho qobelloa ho ithiba. Ka mokhoa o ts'oanang, Ahmed & Koob (1998) o tlalehile hore likhoto li lumelletsoe ho itšebelletsa IV cocaine bakeng sa 6 hd − 1 (phihlello e atolositsoeng), empa eseng 1 hd − 1 (phihlello e lekanyelitsoeng), e hlahisitse boits'oaro bo joalo ka bokhoba. Tsena li ne li kenyelletsa keketseho ea phepelo ea lijo (Ahmed & Koob 1998; Mantsch et al. 2004; Ferrario et al. 2005), ts'usumetso e eketsehang ea ho sebelisa lithethefatsi (Paterson & Markou 2003), a tsoela pele ho batla lithethefatsi le ha a tobane le litlamorao tse mpe (Vanderschuren & Everitt. 2004; Pelloux et al. 2007) le tšekamelo e kholo ea ho khutlisetsoa mosebetsing (Ahmed & Koob 1998; Ferrario et al. 2005; Knackstedt & Kalivas 2007). Tse ling tsa litlamorao tsena le tsona li hlalositsoe kamora phihlello e atolositsoeng ea heroine (Ahmed et al. 2000).
(a) Liphoso tsa kelello kamora phihlello e atolositsoeng
Phihlello e atolositsoeng ea "cocaine" e boetse e hlahisa matšoao a ho se sebetse ha cortex ea pele ho liphoofolo, ho bonahala e ts'oana le tse tlalehiloeng ho batho ba lemaletseng bophelo (Jentsch & Taylor 1999; Rogers et al. 1999). Mohlala, Briand et al. (2008) haufinyane o fumane phokotso e sa khaotseng ea dopamine D2 (eseng D1) receptor mRNA le protheine ka har'a medial prefrontal cortex ka likhoto tse fuoeng katoloso, empa e sa lekanyetsoe, phihlello ea cocaine (0.4 mg kg − 1 ka ente), e tsamaeang le likhaello tse sa khaotseng mosebetsing o tsepamisitseng maikutlo o neng o supa ho fokotseha ha maemo a kelello. George le al. (2007) ba tlalehile hore phihlello ea k'hok'heine e atolositsoeng, empa e se na moeli (0.5 mg kg − 1 ka ente) e hlahisitse likhaello mosebetsing oa mohopolo o sebetsang o hlokang kotlo e ka pele, e neng e amahanngoa le liphetoho tsa lisele sebakeng seo sa boko. Kamora nako, re sebelisa litekanyetso tse phahameng (0.75 mg kg-1 ka ente), Calu et al. (2007) o fumane hore likhoto li lumelletsoe ho itšebelisetsa cocaine bakeng sa 3 hd-1 e bonts'itse likhaello tse sa khaotseng thutong e khutlelang morao.
Ka kakaretso, hona joale ho na le bopaki bo bongata ba hore ho fihlela ts'ebeliso ea lithethefatsi ho thusa nts'etsopele ea matšoao a kang a bokhoba le bofokoli ba kelello ba liphoofolo. Sena se etsahala hobane phihlello e atolositsoeng e nolofalletsa tšebeliso e kholo ea lithethefatsi ho feta phihlello e lekanyelitsoeng, mme e hlahisa liphetoho tse lekanang bokong tse ikarabellang bakeng sa boits'oaro bo joalo ba ho lemalla (Mantsch et al. 2004; Ahmed et al. 2005; Ferrario et al. 2005; Briand et al. . 2008).
(b) Na phihlello e atolositsoeng ea "cocaine e tsamaisang" e hlahisa maikutlo?
Khopolo ea ts'usumetso ea maikutlo e khothaletsa hore liphetoho tse amanang le maikutlo li bohlokoa bakeng sa phetoho ho tloha ho ts'ebeliso e mpe ea ts'ebeliso ea lithethefatsi. Ka hona, ha ho latela hore na mekhoa ea ho fihlella e atolositsoeng e fana ka mefuta e metle bakeng sa phetoho ena, re ka bolela esale pele hore phihlello e atolositsoeng e boetse e lokela ho hlahisa maikutlo a matla a boitšoaro le liphetoho tse amanang le tsona bokong. Re na le bopaki ba ho fana ka maikutlo a hore ehlile ho joalo. Ferrario et al. (2005) o ile a lumella likhoto hore li fihle kahare ho koaeine (6 hd − 1 bakeng sa approx. Libeke tse tharo) ebe li ile tsa lekoa kamora nako, khoeling e le ngoe kamora ho pepesetsoa lithethefatsi. Likhoto tse neng li atisitse phihlello ea koae li bontšitse maikutlo a matla ho feta likhoto tse fuoang phihlello e fokolang (1 hd) 1), le liphetoho tse amanang le matla a kelello: keketseho e kholo ea letsoalo la methapo ea methapo methapong ea methapo e bohareng ea kutlo. bokaholimo ba li-nucleus accumbens. Keketseho e joalo ea letsoalo la lesapo la mokokotlo ka kotloloho mokokotlong oa li-accumbens e kile ea amahanngoa le nts'etsopele ea psychomotor sensitization (Li et al. 2004).
Ka lehlakoreng le leng, haeba liphetoho tse amanang le khothatso bokong li ka baka ho lemalla, ho ka boleloa esale pele hore kalafo e matlafatsang pele ho ts'ebeliso ea lithethefatsi e tla thusa nts'etsopele e latelang ea boits'oaro bo joalo ka litoeba ha likhoto li fuoa phihlello ea lithethefatsi. Hona ho bonahala ho le joalo. Re fumane hore mofuta oa kalafo ea amphetamine o hlahisitseng maikutlo a kelello o potlakisa keketseho e latelang ea tšebeliso ea k'hok'heine, ha liphoofolo hamorao li lumelloa ho iketsetsa cocaine (Ferrario & Robinson 2007). Ehlile, joalo ka ha ho boletsoe kaholimo, kalafo e phetoang ka lithethefatsi tse 'maloa e eketsa tšusumetso e latelang ea lithethefatsi (Vezina 2004; Nordquist et al. 2007), hape e nolofalletsa nts'etsopele ea litloaelo tsa S-R, e leng sesupo sa bokhoba (Nelson & Killcross 2006; Nordquist et al. 2007). Liphuputso tsena li fana ka maikutlo a hore liphetoho tsa methapo ea kutlo tse matlafatsang maikutlo li kanna tsa lekana ho khothaletsa boits'oaro bo ts'oanang le joala.
Leha ho le joalo, ho bohlokoa ho hlokomela hore ho na le pherekano lingoliloeng mabapi le hore na phihlello e atolositsoeng ea k'hok'heine e itšebetsang e hlahisa maikutlo a kelello. Litlaleho tse 'maloa li re phihlello e atolositsoeng ea "cocaine" e hlahisa maikutlo a kelello, empa ha ho na ts'ehetso e kholo ho feta phihlello e lekanyelitsoeng (Ahmed & Cador 2006; Knackstedt & Kalivas 2007), mme ho na le tlaleho e le' ngoe e ekelitseng phihlello e fella ka 'tahlehelo' ea sensitization Ben-Shahar et al. 2004). Empa lithuto tsena tsa morao-rao e kanna ea ba li ile tsa lekanya boits'oaro bo fosahetseng: boits'oaro ba boits'oaro bo hlalositsoe hanyane ka hanyane e le keketseho ea tšebetso ea locomotor feela. Liphuputso li ile tsa hloleha ho lekanya boits'oaro bo bong bo bonts'ang maikutlo a matla le ho feta a kelello (mohlala, ho hlaha ha liphetoho tsa boits'oaro, ho kenyeletsoa le maikutlo a mabe a likoloi, ao maemong a phahameng a qothisanang lehlokoa le tlholeho). Tumellanong le lithuto tsena, ha rea fumana phapang ea phapang ea phihlelletso e lekanyelitsoeng ha e bapisoa le ts'ebetso ea locomotor e le eona feela mohato o sebelisitsoeng (Ferrario et al. 2005). Empa, ka nako e ts'oanang, re fumane hore phihlello e atolositsoeng ea k'hok'heine e hlile e hlahisitse ts'ehetso e matla ea kelello ho feta phihlello e lekanyelitsoeng ha ho sisinyeha ha hlooho ho hlohlellelitsoeng ke lithethefatsi le hona ho lekantsoe. Joalokaha ho bontšitsoe khale ke Segal (1975, leq. 248), e mong oa bo-pula-maliboho ba etsang lipatlisiso mabapi le ts'ehetso ea boits'oaro, 'ho khetholla likarolo tse fapaneng tsa karabelo ea boits'oaro hoa hlokahala hobane litlamorao tsa lithethefatsi ho boits'oaro li kanna tsa amana le tlholisano'. Mehato ea locomotor ka boeona hangata ha e tsotelle phetoho e tsoang ho boits'oaro bo laoloang ke locomotion ea pele ho ea ho tse amanang le maikutlo a makoloi, joalo ka ha ho matlafatsoa ka matla (Segal 1975; Post & Rose 1976), mme ka hona ts'ebeliso e le 'ngoe feela ea boits'oaro ba locomotor e le index ea psychomotor khothatso e ka lebisa liqetong tse fosahetseng.
Tlhaloso e fetelletseng ea liphetho tse mpe maemong a kang ana e ka hlasela tšimo hobane liphetho tse mpe li haufi le ho sitoa ho hlalosoa ntle le tlhaiso-leseling e eketsehileng. Ke maemong a litholoana tse ntle feela moo mohato o le mong joalo ka locomotion o le mong o ka etsang qeto. Flagel & Robinson (2007) o pheta ntlha ena haufinyane, a bonts'a hore, ka lethal dose, ho kanna ha se be le phapang ea sehlopha liketsahalong tsa locomotor tse bakoang ke k'hok'heine (mohlala, sebaka se tsamaeang kapa li-crossovers), empa phapang e kholo ea sehlopha ka bobeli ba mofuta oa locomotion ( Lebelo la sekhahla se seng le se seng sa khatello ea maikutlo) le mekhoeng e meng ea boitšoaro (mohlala, makhetlo le palo ea motsamao oa hlooho; bona Crombag et al. (1999) le Flagel & Robinson (2007) bakeng sa puisano e batsi ea taba ena). Liphuputso tsa nako e tlang tsa ts'ehetso kamora ho fihlella nako e telele li ka una molemo ka ho hopola hore ho matlafatsa ho ka hlaha ka litsela tse fapaneng le ho metha tse fetang e le 'ngoe.
6. NA LITLHAKISO TSA BOPHELO BA LIJO TSA LITLHAKISO TSE KHOLO LI FIHLETSA LITLHAHISO TSA BORAPELI?
Phehisano e 'ngoe e tšoenya hore na ho ka etsahala hore ho hlahisoe phetoho bokong le boits'oarong ho liphoofolo tse amanang le tšebeliso ea lithethefatsi tsa motho ha lithethefatsi li fanoa ke motho ea lekang, ho e-na le ho tsamaisoa ke phoofolo. Ha u nahana ka sena, ho ka ba bohlokoa le ho feta ho hlahloba ho tšoana ha sephetho sa matšoao a bokhoba ba batho ho feta mokhoa oa tsamaiso. Ho joalo, mefuta ea ts'ebetso kapa mekhoa e loketseng ka ho fetisisa ke e hlahisang sephetho sa boitšoaro, sa kelello kapa sa neurobiological se ts'oanang hantle le tse tlisoang ke bokhoba ba batho. Mme ka hona, potso ke hore, ke lits'ebetso life tse ka etsang see ho liphoofolo?
Re fana ka maikutlo a hore lithethefatsi tse itekang le tse itšebetsang li ka hlahisa litholoana tse nepahetseng, ha feela li ka hlahisa ts'usumetso ea methapo. Ha e le hantle, motho a ka etsa nyeoe bakeng sa tlhahiso e matla le ho feta: hore lits'ebetso tse sebelisoang ke liteko tsa liteko tsa lithethefatsi tse hlahisang ts'ehetso e matla li ka etsa ka mokhoa o atlehileng ho lemalla lithethefatsi ho feta mekhoa ea boits'oaro e sa atleheng ho hlahisa ts'ehetso e matla (joalo ka lits'ebetso tse fokolang tsa phihlello ). Mohlala, boipheliso bo fokolang ba boipheliso bo ka hloleha ho hlahisa khothatso e matla kapa matšoao a bokhoba, joalo ka ha ho boletsoe kaholimo. Ka lehlakoreng le leng, kalafo e matlafatsang ka lithethefatsi tse sebelisitsoeng ke liteko li lekane ho hlahisa tšusumetso e eketsehileng bakeng sa moputso oa lithethefatsi (Vezina 2004), khothatso ea ts'ehetso ea maikutlo a batlang (Robinson & Berridge 2000; Di Ciano 2007), ho holofala hoa kelello (Schoenbaum & Shaham 2008) le S e matla -R litloaelo (Miles et al. 2003; Nelson & Killcross 2006), tseo kaofela li ka tlatsetsang phetohong ea bokhoba. Ntle le moo, sethethefatsi se laoloang ke liteko se bakang ts'isinyo se fetola boko ka litsela tse amanang le tšekamelo ea ho khutlela morao, joalo ka ho matlafatsa tokollo ea glutamate mokokotlong oa li-accumbens (Pierce et al. 1996). Sensitization e hlohlellelitsoeng ke lithethefatsi tse sebelisitsoeng ke liteko e bile e bonts'a mofuta oa 'incubation effect' (e hola ka nako ea ho ithiba ntle le lithethefatsi; Paulson & Robinson 1995) e bonahalang e nolofalletsa tšekamelo ea ho khutlela morao (Grimm et al. 2001), mme e ka khona potlakisa keketseho ea tšebeliso ea lithethefatsi (Ferrario & Robinson 2007). Ka hona, ho a khonahala hore, tlasa maemo a lebisang tlhokomelong e matla, lithethefatsi tse fuoang liteko li kanna tsa se sebetse feela ho hlahiseng sephetho sa boitšoaro, kelello kapa methapo e amanang le bokhoba ba tahi, empa hape e ka sebetsa le ho feta mekhoa ea boipheliso e sa atleheng. ho hlahisa khothatso e matla.
Ho kanna ha ba le mabaka a mangata a sena, empa e ka ba hore mekhoa e meng ea boipheliso ha e sebetse haholo ho hlahiseng liphetoho tse matla tse amanang le maikutlo a bokong. Lintho tse ngata tse sebelisanang li susumetsa hore na ho pepesehela sethethefatsi ho hlahisa liphetoho tse amanang le ts'ehetso bokong, ho kenyeletsoa lethal dose, palo ea likotsi, mokhoa oa ho pepeseha (nako e khutšoane), sekhahla sa tsamaiso ea lithethefatsi, maemo ao setlhare se nang le boiphihlelo ho sona, jj. Nka feela likhaohano-liente tse fanoeng haufi ka nako ha li na thuso ho hlahiseng maikutlo (Post 1980; Robinson & Becker 1986). Sena e kanna ea ba lebaka la lits'ebetso tse fokolang tsa boipheliso tse fanang ka ts'ehetso e nyane haholo: sena se ka hlahisa keketseho e ts'oarellang ea li-plasma tsa cocaine nakong eohle ea teko, e sa nepahalang bakeng sa ho hlahisa ts'ehetso. Ehlile, lihora tse 6 tsa phihlello e atolositsoeng ka letsatsi le leng le le leng le tsona li ka baka maemo a tsitsitseng a lero la mali, empa maemong ana keketseho ea phepelo, le bongata ba sethethefatsi seo qetellong se ka sebelisoang, li ka sithabetsa mabaka a mang a neng a ka fokotsa ts'ehetso. Tsamaiso ea liteko e ka qoba maemo ao a fokolang ka ho kopanya litekanyetso tse phahameng haholo le kalafo ea nakoana (Robinson & Becker 1986). Ebile, sena se ka nka boemo bo betere pejana ho nts'etsopele ea bokhoba ba tahi ha ts'ebeliso ea lithethefatsi e ka ba e sa nepahalang ebile e le nakoana.
7. MOKHATLO OA LITLHAKISO TSA TLHAKISO TLHALOSO: HO BATLA VERSUS KOPA?
Lithethefatsi tse ngata tse ka lemalloang qalong li hlahisa maikutlo a thabo (nyakallo), e khothaletsa basebelisi ho sebelisa lithethefatsi hape. Leha ho le joalo, ka phetoho ea ho lemalla lithethefatsi, ho bonahala ho na le ho fokotseha ha karolo ea menyaka ea lithethefatsi. Ho ka etsahala joang hore lithethefatsi li batloe le ho feta leha li se li ratoa hanyane? Ho ea ka khopolo ea khothatso ea khothatso, lebaka la ho ikhanyetsa hona ke hobane ts'ebeliso e mpe ea lithethefatsi e matlafatsa feela litsamaiso tsa methapo tse tsamaisang ts'ebetso ea ts'usumetso ea ho hlohlelletsa (ho batla), empa eseng litsamaiso tsa methapo tse buellanang le litlamorao tse khahlisang tsa lithethefatsi (ho rata). Kahoo, tekanyo eo lithethefatsi li batloang ka eona e eketseha ka mokhoa o sa lekanyetsoang ho isa tekanyong eo li ratoang ka eona mme karohano ena lipakeng tsa ho batla le ho e rata e ntse e eketseha butle-butle ka kholo ea bokhoba ba tahi. Ho ikarola lipakeng tsa ho batla le ho rata ho rarolla qaka e seng e lebisitse ho bo-ramahlale ba bang ba methapo ea maikutlo ho fihlela qeto ea hore 'ponelopele e le' ngoe e hlahelletseng ea maikutlo a ts'usumetso e ka ba hore, ka ts'ebeliso e phetoang, ba lemalloang ba ka sebelisa sethethefatsi se fokolang '(Koob & Le Moal 2006, leq. EA-445). Ehlile, hoo ho fapane le seo re se bolelang esale pele: haeba ts'ehetso e etsa hore ba lemalloang ba batle lithethefatsi tse ngata, ba lokela ho noa lithethefatsi tse ngata, eseng hanyane.
Ka tsela e amanang empa e fapaneng, karohano ea ho batla ho ratoa e boetse e lokolla taolo ea bokhoba ba tahi hore e se ke ea khannoa ke dysphoria e mpe e atisang ho latela ho emisoa ha ts'ebeliso ea lithethefatsi, bonyane matsatsi a seng makae kapa libeke. Lits'ebeletso tsa ho hula li ka kenya letsoho ho nka lithethefatsi ha li ntse li le teng (Koob & Le Moal 2006). Empa bokhoba ba tahi bo ntse bo tsoela pele nako e telele kamora ho ikhula. Liphetoho tse amanang le sensitization bokong, tse ka tsoelang pele nako e telele kamora ho khaotsa, li fana ka mokhoa oa ho hlalosa hore na hobaneng ba lemaletseng ba ntse ba batla lithethefatsi 'me ba ka ba le monyetla oa ho khutlela mokhoeng leha ba se ba qetile nako e telele ba sa li tlohele, esita le ha ho se na boemo bo bobe.
8. KHOTSO
Qetellong, bokhoba ba tahi bo kenyelletsa liphetoho tse tlisoang ke lithethefatsi lipotolohong tse ngata tse fapaneng tsa boko, tse lebisang liphetohong tse thata tsa boits'oaro le ts'ebetso ea kelello. Re phehile khang ea hore liphetoho tsa mantlha tse lebisang bokhobeng li ba teng ha ts'usumetso ea ts'usumetso e kopana le bofokoli ba ho etsa liqeto ka kelello le sephetho sa 'tahlehelo ea taolo e thibelang boitšoaro le kahlolo e fosahetseng, e kopantsoe le ho matlafatsa tšusumetso ea ba lemaletseng ho fumana le ho sebelisa lithethefatsi, e etsa bakeng sa motswako o ka bang kotsi '(Robinson & Berridge 2003, maq. 44-46). Kahoo, re matlafalitsoe ke bopaki bo bokelletsoeng lilemong tsa morao tjena, re lula re kholisehile ho fihlela qeto ea hore 'bothateng ba eona, ho lemalla joala ke bothata bo susumelletsang batho ho ba le ts'oaetso ka lebaka la ts'usumetso e bakoang ke lithethefatsi ea litsamaiso tsa methapo ea kutlo tse supang hore ho na le boiphihlelo bo itseng. E ka bakoa ke lits'oants'o tsa lithethefatsi joalo ka karabelo e ithutoang e susumetsang ea boko, empa ha se bothata ba ho ithuta ka mokhoa o sa tloaelehang ka bonngoe. Hang ha e se e le teng, ho batla ho khothalelitsoeng ho ka qobella ho lelekisa lithethefatsi hore na ebe motho ea lemaletseng joala o na le matšoao a ho tlohela kapa che. Hobane ho ba le boikhohomoso ho fapane le monyaka kapa ho rata lits'ebetso, ts'ehetso e fana ka sethethefatsi se potlakileng se batlang bophelo bo mamellang '' (Robinson & Berridge 2003).
LINTLHA TSA LITLHAHO
Patlisiso e entsoeng ke bangoli e tšehelitsoe ke lithuso tse tsoang ho National Institute on Drug Abuse (USA).
Tlatsetso e le 'ngoe ea 17 Tlatsong ea Seboka sa Puisano' Mokhoa oa ho ba le bothata ba ho lemala: lits'ebeletso tse ncha '.
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