Dopamine Hypothesis ea Lithethefatsi Tsa Lithethefatsi le Bohlokoa ba Ts'oaetso ea Ts'oaetso (2011)

Psy Psychology. 2011; 2: 64.

PMCID: PMC3225760
Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

inahaneloang

Phetisetso ea Dopamine (DA) e anngoe haholo ke lithethefatsi tsa tlhekefetso, 'me liphetoho mesebetsing ea DA li ameha maemong a fapakaneng a tlhekefetso ea lithethefatsi le monyetla oa tšebeliso e ka bang teng. Haholo-holo, lithuto tsa mantlha li tlaleha ho fokotseha hoa ts'ebetso ea motlakase oa li-neuron tsa joala ho joala, opiate, cannabinoid le likhoto tse ling tse ts'epahalang lithethefatsi. Ho feta moo, ho lokolloa ha DA ho Nuklea (Nacc) ho fokotsehile hoo e batlang e le litoeba tsohle tse itšetlehileng ka lithethefatsi. Ka tsela e tšoanang, lithuto tsena li ts'ehetsoa ke likhahla tsa intracranial self stimulation (ICSS) nakong ea ho khaotsa joala, nicotine, opiates le lithethefatsi tse ling tsa tlhekefetso, ka hona li fana ka maikutlo a hypofunction ea neural substrate ea ICSS. Ka hona, litlhahlobo tsa morphological tse kenyellelitsoeng tlhahlobisong ea netefatso ea methapo ea kutlo e bohareng ea Nacc, mphato oa post-synaptic oa li-terminals tsa DA, li bonts'a liphetoho tse kholo sebopeho le ts'ebetsong ea sisteme eohle ea mesolimbic. Tumellanong le liphumano tsena, liphuputso tse entsoeng ke batho li bonts'itse phokotso ea li-receptor tsa dopamine tse tsamaeang le tokollo e nyane ea DA ea semmuso setulong sa "cocaine" sa heroin, le litaba tse amanang le joala.dopamine-ea futsanehile ” kelello e lemaletseng ea motho. Phokotso e sa feleng ea tšebetso ea 'mele ea sistimi ea DA e lebisa mohopolo oa hore keketseho ts'ebetsong ea eona, ho khutlisa maemo a pele ho lithethefatsi, e ka hlahisa ntlafatso e kholo ea kliniki (ho fokotsa ho lakatsa, ho khutla hape, le ho tsoma lithethefatsi / ho nka lithethefatsi). Ka mohopolo, e ka fihlelleha ka meriana le / kapa ka ho kenella ka lipale tse kang ho ts'oaroa ha matla a boloi (TMS). Tlhahiso ea eona ea anatomo-physiological e le thuso e ka thusang ea ho phekola bokhoba ba joala le lithethefatsi tse ling e tla hlalosoa le ho hlahisoa e le sebopeho sa thuto se lokelang ho etsoa tlhahlobo ea liteko ho batho ba lemaletseng lithethefatsi.

Keywords: ho lemalla, dopamine, rTMS, li-dopamine agents, VTA, preortal ea cortex

Bokhoba ba lithethefatsi ke bokuli bo hlahisang liphetoho tse tebileng mekhoeng ea batho (Hyman, 2007; Koob le Volkow, 2010), ka litlamorao tsa bohlokoa tse fapaneng maemong a fapaneng, ho kenyelletsa bophelo bo botle ba motho, mosebetsi, tšebelisano ea lelapa, le sechaba ka kakaretso (Chandler et al., 2009). Monyetla oa kalafo bakeng sa bokuli bona bo sithabetsang, ntle le mekhelo e sa tloaelehang, e lekantsoe ho kalafo ea pharmacologic e sa khotsofatseng haholo (Koob et al., 2009; Leggio et al., 2010; Potlako, 2010). Ho tloha mona tlhokeho ea ho theha kalafo e ncha ea kalafo / ts'ebetso e ikemetseng ho tseo hangata li sebetsoang.

Transcranial sumimous (TMS), ka ho phatloha hoa tšimo ea elektronegnetic e khonang ho tšela ka mokhoa o se nang letho ka lehata le ho susumetsa ntho e ka tlasa bokong, e bonahala e le moemeli ea ts'episang bakeng sa ho phekola boits'oaro bo tlatsetsang (Barr et al., 2008; Feil le Zangen, 2010le mafu a mang a boko (Kobayashi le Pascual-Leone, 2003). Ka bokhutšoanyane, mokhoa ona o mocha o lumella ho fetoloa hoa likarolo tse sa bonahaleng tsa bokong ba motho ea falimehileng le ea hlokolosi eo a ntseng a ithuta. Lekala la motlakase la pulsatile le hlahisoang ho potoloha lekhopho le tšela lehata mme le khona ho hlasimolla / ho thiba li-neurons ka kotloloho (Padberg le George, 2009). Hangata e sebelisoa e le sesebelisoa sa ho etsa lipatlisiso, TMS haufinyane e tiisa karolo ea eona e le mokhoa oa ho phekola o ka ananeloang ke Tsamaiso ea Lijo le Lithethefatsi bakeng sa methapo ea kelello joalo ka khatello ea maikutlo e hanyetsang lithethefatsi, lefu la ho ferekana kelellong le matšoao a mabe a schizophrenia. Sebakeng sa ts'ebeliso ea lithethefatsi, monyetla oa kalafo oa TMS o lekoa lithutong tse itšetlehileng ka nicotine (Lang et al., 2008; Amiaz et al., 2009), lithethefatsi tsa koae (Boutros et al., 2001, 2005; Sundaresan et al., 2007; Politi et al., 2008), le matahoa (Conte et al., 2008; Mishra et al., 2010). Leha diphetho li hlile li khothatsa, ho se lekane ha liphetho tsa tlhahlobo tse hlahlojoang lithutong tse fapaneng le phapang ea sebopeho / sebaka / mokhoa oa ts'usumetso o thibela ho bapisoa ka kotloloho le ho sitisa liqeto tse tiileng. Leha ho le joalo, lithutong tseo ho tsona takatso e neng e lekantsoe (Politi et al. 2008; Amiaz et al., 2009; Mishra et al., 2010) phokotso ea bohlokoa e fumanoe, ka hona e khothaletsa tlhahlobo e eketsehileng ea liteko. Hajoale, re ntse re lekola tšebeliso ea matla ea taolo ea taolo ea taolo ea tahi le taolo ea joala (Addolorato et al., Ka ho itukisetsa), nako e telele le e telele ea k'hok'heine ea koae ka ts'ebeliso ea lithethefatsi tsa "cocaine" (Pedetti et al., Ka ho itukisetsa) , le chelete / khetho ea cocaine lithutong tsa lab tsa kalafo ea lithethefatsi tsa koae e sa batleng (Martinez et al., ha a ntse a itokisetsa). Leha ho le joalo, sebaka sa boko (s) sa ho ts'oaroa / ho thibeloa le litekanyetso tsa ho hlasimolla (ke hore, linako tse ngata tsa ho khothatsa, palo ea seboka, joalo-joalo) ke litaba tsa ngangisano e kholo 'me ho hlokahala mabaka a bohlokoa.

Dopamine e le Monyetla o ka bang oa Phekolo

Karolo ea litsamaiso tse bohareng tsa DA litlamorao tse mpe tsa lithethefatsi tsa tlhekefetso e ile ea amoheloa khale (Wise, 1980, 1987; Di Chiara le Imperato, 1988). Le pele ho moo (Ahlenius et al., 1973), ho entsoe boiteko ba ho thibela euphoria e bakoang ke joala ka ts'ebetso ea DA synthesis inhibitor alpha methyl-para-tyrosine. Le ha theoretically ineccepibile, mokhoa ona (phokotso ea li-DA tse eketsoang lithethefatsi ho thibela tlhekefetso) ha o na monyetla oa ho ba le tumellano e sebetsang joalo ka karolo efe kapa efe e nang le lihanyetsi tsa DA (ke hore, li-neuroleptics) thepa e tsejoa e le ntho e hohelang batho. Ka lehlakoreng le leng, bopaki ba liteko bo fumanehang ka bongata bo fana ka maikutlo a hore mesolimbic dopamine system ke "hypofunctional" bokong bo lemaletseng (Melis et al., 2005). Ka bokhutšoanyane, phehisano ea maikutlo e fokotseha ts'ebetso ea DA e fokotsehileng lithutong tse lemaletseng e baka phaello e fokotsehileng ho litheko tse sa amaneng le lithethefatsi le ho eketsa kutloisiso ea lithethefatsi tsa khetho (Melis et al., 2005), e lebisang ho tlhahiso ea hore ho khutlisetsa ts'ebetso ea DA e kanna ea ba molemo haholo.

E itšetlehile ka joala (Boemong ba hona joale poleloana "ho its'epa," ha ho buuoa ka taba ea tlhahlobo eo eseng motho, e bonts'a boemo boo ho eona taba e bontšitseng ntle ho tikatiko bopaki ba ho its'epaha, ke hore, matšoao a ho khaotsa) likhoto li bontša phokotso e kholo ea sekhahla sa ho thunya se ikemetseng le ho thunya ho hoholo ha linokoane tse senotsoeng tsa Nucleus (Nacc) - ho kenya sebaka sa li-neurral tegmental (VTA) se nang le li-neurons tsa DA ka har'a li-rats (Diana et al., 1993) le litoeba (Bailey et al., 2001) e bakang phokotso e tšoanang ea li-Microdialysate DA ho Nacc (Rossetti et al., 1992; Diana le al., 1993; Barak et al., 2011). Ho feta moo, ts'ebetso e fokotsehileng ea dopaminergic e hlahisa matšoao a ho khaotsa joala (Diana et al., 1996, 2003) ka hona ho fana ka maikutlo a karolo bakeng sa DA liphellong tse sa feleng tsa ts'ebeliso ea lino tse tahang ha e sa kenyeletse monyetla oa karolo ea DA maemong a itseng a ho tlohela. Ho feta moo, maemo a DA (a pele-ho itšetleha) a DA ho Nacc a khutlisoa ha ethanol e le boithati (Weiss et al., 1996) le / kapa ba laetsoeng ka mokhoa o patehileng (Diana et al., 1993, 1996). Lipatlisiso tsena li bapisoa le lithuto tsa intracranial self stimulation (ICSS) tse bonts'ang hore litoeba tse tlositsoeng ke ethanol li khona ho boloka boits'oaro ba ICSS ha feela matlafatso a hona joale a eketsehile (Schulteis et al., 1995). Tlhahlobo ena ea bohlokoa e bonts'a ka matla hore karoloana ea neural e ikarabellang bakeng sa ho boloka boits'oaro ba ICSS e matlafalitsoe, kapa e hana hape, ka taba e itšetlehileng ka joala ha e bapisoa le taolo ea eona. Kaha neural substrate ea ICSS e kenyelletsa li-axons tsa DA (Yeomans, 1989; Batho ba bang et al., 1993) haufi le electrode e hlasimollang, liphetho li tlatsana le tse tlalehiloeng ka holimo mme li ts'ehetsa hantle ts'ebetso e haellang ea li-neuron tsa DA. Ntle le moo, tiisetso ea phokotso ea ts'ebetso ea DA (ntle le qeto ea matšoao a ho khaotsa) e boetse e ngotsoe litlalehong tse itšetlehileng ka morphine (Diana et al., 1999), ha dichotomy pakeng tsa ts'ebetso ea DA le ho khaotsa ka mokhoa o itseng e se e bonoe ho litoeba tse khaotsoeng tsa cannabinoid (Diana et al., 1998). Ka mokhoa o ts'oanang, ho tlosoa ha heroin e nang le maemo ho fokotsa kutloisiso ea moputso (Kenny et al., 2006) e phehellang hantle ntle le karolo ya pele ya ho tlohela. Liphumano tsena, tse bonoang metseng eohle e fapaneng ea tlatsetso le liteko, li fana ka maikutlo a hore khatello ea DA e phehella ka nako, leha e khutlela ho "tloaelo" (Diana et al., 1999, 2006), qetellong ka mefuta e ikhethileng ea nako ea nako.

Ntle le lingoliloeng tsa mantlha, litlaleho ho batho le tsona li ts'ehetsa karolo e nyenyefalitsoeng ea phetisetso ea DA ho lino tse tahang. Ha joala bo eketsa tokollo ea DA lithutong tse phetseng hantle (Boileau et al., 2003) ka phapang e itseng ea bong (Urban et al., 2010), palo e fokotsehileng ea li-receptor tsa DA e hlokometsoe (Volkow et al., 1996; Martinez et al., 2005) lits'ebetsong tsa lino tse tahang tse shebahalang li tsamaisana le ho lokolloa ha DA (Martinez et al., 2005, 2007; Volkow et al., 2007). Leha palo e fokotsehileng ea li-receptor tsa DA e ka ba, qalong ho bonoa, e nkoa e fana ka maikutlo a e eketsehile Ho lokolloa ha DA, ho lokela ho hopoloa hore ka ho tsamaisa DA inhibitor alpha methyl-para-tyrosine, Martinez et al. (2009) ba ile ba khona ho khetholla monyetla ona. Ho joalo, le ha taolo e phetseng hantle e bonts'a ho eketseha ha raclopride ka mor'a taolo ea papo ea alpha methyl-para-tyrosine, lithuto tse itšetlehileng ka koae ha li (kapa ka tekanyo e fokolang haholo; Martinez et al., 2009). Liphetho tse tšoanang li fumanoe ka dopamine e lokollang moemeli methylphenidate (Volkow et al., 2007) le amphetamine (Martinez et al., 2005) ho matahoa a joala. Haholo-holo, ka boqhetseke ho eketsa maemo a bokong a li-receptor tsa DAD2, ka ho sebelisa seteraeke se kopanyang sa adenoviral se kentsoeng karolo ea cDNA ho DAD2 ho Nacc, e fokotsa tšebeliso ea joala ho noeng litheko ka mokhoa o ikemetseng, ka tsela eo e fana ka phephetso ea hore ts'oaetso ea phetisetso ea DA e ka ba le molemo litlamorao ho ho batla joala le ho tsumwa joala, mehlaleng ea liteko (Thanos et al., 2001, 2004). Tumellanong le sephetho sena, palo e phahameng ea boiketsetso ea li-receptor tsa DA D2 e ​​bontšitsoe hore e na le karolo ea ts'ireletso ho litho tse sa jeleng joala tsa malapa a joala (Volkow et al., 2006). Liphetho tsena li ts'ehetsa taba ea hore palo ea li-receptor tsa DA (mme ka lebaka leo phetisetso ea DA) e tsamaisana hantle le ho nooa.

Maikutlo ana a ka supa hore "oa eketseha ” Li-neuron tsa DA ho hlahisa DA e fumanehang ho feta ka har'a fereko ea synaptic li ka fokotsa mats'oao a mang a ho lemalla le bokhoba ba tahi, ka ho etsa joalo ba ka ba le semelo sa kalafo. Ka khopolo-taba, sena se ka fihlelleha ka maano a mabeli a fapaneng: (1) Lithethefatsi tse nang le tšebeliso ea DA le (2) TMS. Ka bobeli menyetla e tšohloa ka tlase.

Lithethefatsi tse fanang ka litlatsetso

Leha meriana e eketsang ts'ebetso ea DA e ka sebetsa hantle ho phekola mafu a tlhekefetso ea joala, litholoana tse hanyetsanang li hlahisitsoe (Swift, 2010). Mohlala, ho fanoe ka tlhahiso ea hore bronocristine ea DA e fokotsa ho tahoa ho lino tse tahang (Lawford et al., 1995), empa phuputso e hlophisitsoeng e sa sebetseng, e sa boneng mahlo hape e sebelisang sebaka se sebelisang nako e telele bakeng sa ente ea bromocriptine ho batho ba 366 ba lemaletseng joala ha baa ka ba fumana phapang ea ho khutla hoa joala pakeng tsa meriana le placebo (Naranjo et al., 1997). Mohlala o mong ke oa morafinil oa meriana o hlasimollang (DA e sa tobang agonist), o fumanoeng o ntlafatsa kutloisiso ea batho ba 40 ba lemaletseng tahi ba nang le organic brain syndrome, empa litlamorao tsa ho nooa ha li na ho lekanngoa (Saletu et al., 1990). Leha ho le joalo, modafinil e fokotse ts'ebeliso ea koae ka ho ithuta ka mokhoa o laoloang ke placebo le batho ba 62 ba itšetlehileng ka koae (Dackis le O'Brien, 2005), ha teko e 'ngoe e sa fumane liphapang pakeng tsa modafinil le placebo tse lekiloeng ho basebelisi ba methamphetamine (Shearer et al., 2010). Leha bopaki ba ts'ebeliso ea lingaka tsa DA e le kalafo bakeng sa mathata a joala le / kapa a ts'ebeliso ea lithethefatsi bo sa lumellane (Swift, 2010), ho bile le thahasello e tsosolositsoeng bakeng sa lithethefatsi tsena, mohlomong hobane maikutlo a lekaneng a neurobiological (Melis et al., 2005) e se e fumaneha. Mohlala, aripiprazole (Semba et al., 1995; Burris le al., 2002; Shapiro et al., 2003) ngaka ea karolo e lekanang ea DA eo ka molao e lokelang ho qabanya DA ha molumo o phahame, athe e lokela ho eketsa phetiso ea DA ha molumo oa motheo o le tlase, e emela kalafo e reriloeng bakeng sa mathata a tlhekefetso ea joala (Kenna et al., 2009). Boithuto ba joala ba batho ba laboratori bo bontšitse hore aripiprazole e fokotsa ho nwa (Kranzler et al., 2008), haholoholo ho joala bo kenang haholo (Voronin et al., 2008). Phuputso ea fMRI e bonts'itse hore aripiprazole haholo e fumana ts'ebetso ea neural ka har'a "ventral striatum" ho arabela litheko tsa joala (Myrick et al., 2010) ka hona ho fana ka tlhahiso ea menyetla ea kalafo e ka bakang ho khutla hoa moea oa cue-ikiwa. Ho feta moo, tlhahlobo ea kalafo e laoloang habeli ka libeke tse 12 le batho ba lemaletseng joala ba 295 ba fumane hore aripiprazole qalong e fokotse matsatsi a ho nwa haholo ha a bapisoa le placebo, empa phello ena ea bohlokoa e ne e se teng ha lethal dose la 30mg e fihlile (Anton et al., 2008). Teko ena e boetse e bonts'a litla-morao tse kholo le ho khaotsa ho ithuta ka letsoho la aripiprazole, joalo ka ha ho bapisoa le placebo (Anton et al., 2008). Ho khahlisang, tlhahlobo e bulehileng ea "aripiprazole" (Martinotti et al., 2009) le thuto ea morao-rao ea laboratori ea motho (Kenna et al., 2009) e fana ka maikutlo a hore litekanyetso tse tlase tsa aripiprazole (5-15mg ka letsatsi) e kanna ea mamelloa hamolemo mme e ntse e fokotsa ho nwa ka litlamorao tsa ho khutla ho ka bapisoa le tse fumanoeng ka opiate antagonist naltrexone (Martinotti et al., 2009).

Ka kakaretso, dopamine e bapala karolo ea bohlokoa ts'ebetsong ea bokhoba ba tahi, empa litlamorao tse kholo li fokolisitse tšebeliso ea meriana e sebetsang ka kotloloho ho sisteme ea dopaminergic. Ts'ebeliso ea lingaka tsa lefutso tsa DA tse nang le li-profiles tse fokolang tsa litla-morao, le dosing e loketseng li emela tataiso ea bohlokoa bakeng sa lipatlisiso tsa nako e tlang sebakeng sena.

Kholiseho ea Magnetic ea Magnetic

Ho eketsa molumo oa DA ka lisebelisoa tse nepahetseng tsa pharmacological, ke mokhoa o le mong feela o ka khonehang. Ts'ebetso ea tlhaho ea li-neuron tse nang le DA e ka matlafatsoa ka lisebelisoa tse seng tsa bongaka tse kang TMS (Strafella et al., 2001) ka hona, ho fana ka, mantlha, adjunct ho "bongaka ba kalafo" Khahlano le bokhoba, bo fanoang ka litlamorao tse nyane tsa systemic le litlolo tse fokolang. Le ha ho le joalo, le ha taba e le "neurochemical" bakeng sa baemeli ba meriana (li-receptor tsa neurotransmitter, sebaka sa boko jj.,), e tlameha ho thehoa ka boomo bakeng sa TMS. Ho ba ka hore li-neuron tse nang le DA li lutse ka botebo bokong ba kelello (ka hona ho etsa hore li-neurons li se ke tsa khona ho tsamaisa TMS) ha ho khonehe ho li fihlela ka tsela e sa tobang ka li-neuron tse fumanehang kae kae bokong. Dorsolateral prefrontal cortex (DLPfcx) ka ho kenya merero e le mong ka kotlolloho ho rat (Carr le Sesack, 2000) le primate (Frankle et al., 2006) VTA e ka sebeletsa ts'ebetso ena. Lithuto tsena li bonts'a projeke e tlohang ho PFC ho isa ho li-neuron tsa DA tsa mahareng, e khaola ka bobeli ho SN e loketseng le VTA. Li hlaha sebakeng se pharaletseng sa PFC, ho kenyelletsa DLPfcx, cingulate, and orbital cortices. Ho joalo, li-neuron tsena tsa pyramidal (Setšoantšo (Figure1) 1) e ka sebelisoa hampe joalo ka sepheo sa mantlha sa ts'usumetso ea TMS le ts'ebetso ea bona e eketsehang ho hlahisa, qetellong, ntlafatso ea ho fumaneha ha DA ho synaptic cleft ho Nacc. Ka mokhoa o potileng, potoloho e phetheselitsoeng (Setšoantšo (Figure2) 2) e tla ba tse latelang: TMS→DLPfcx→VTA→Keketseho ea DA sebakeng sa probrain projekthi (ke hore, Nacc). Maemong ana, ho bohlokoa ho sebelisa likarolo tsa ho hlasimolla tse amanang le tšebetso ea 'mele ea thuto e ithutoang ho khutlisa maemo a DA a pele ho lithethefatsi. Mohlala, ho bonts'itsoe hore ts'usumetso ea DLPfcx e hlahisa ho phatloha hoa li-neur neur tsa DA (Gariano le Groves, 1988; Murase et al., 1993), e totobatsa bohlokoa ba likarolo tsa ts'usumetso. Ka 'nete, ho thunya ho phatlohileng ho sebetsa hantle ho feta ho ts'ela ka seketsoana (ea mekhahlelo e ts'oanang empa e le e ts'oanang ea lintho tse ling tse ka hare) ho susumetsa tokollo ea DA libakeng tse haufi (Gonon, 1988; Manley et al., 1992). Nako le nako, ho tlalehiloe karolo ea DLPfcx ho laola tšebetso ea DA ka VTA (Taber et al., 1995; Karreman le Moghaddam, 1996).

Setšoantšo sa 1 

Ho aha bocha kopanya ea li-neurons tsa "Golgi-stired pyramidal" tse tsoang DLPfcx tse fumanoeng ke likhakanyo tsa litekanyetso tse 55 bakeng sa botebo ba 27.5μm ho z-e leng. DLPfxc e ka emela sepheo se sebetsang bakeng sa ho hlohlelletsa RTMS.
Setšoantšo sa 2 

Sekema se bontša potoloho e reriloeng ho kengoa tšebetsong ke TMS susumetsang (botala) eo, ka ho kenya ts'ebetso ea pyramidal neuron (e mosehla) ka glutamate ea eona ea neurotransmitter, e ka khahlisang: (1) li-neurons tsa DA tse nang le VTA (bofubelu) le (2) ) MSN ea ...

Har'a lintlha tse fapaneng tse ka bang le tšusumetso ho sebetsa ha ona, bohlokoa ba ts'ebetso ea ts'ebetso ea cortical activation ka tšusumetso ea TMS e bohlokoa (Silvanto le Pascual-Leone, 2008). Ho itšetleha ka mmuso hona ho bohlokoa kaha tšusumetso ea neural ea ts'usumetso efe kapa efe ea kantle e emela ts'ebelisano le ts'ebetso ea boko e tsoelang pele ka nako ea ho hlohlelletsa. Litlamorao tsa tsusumetso efe kapa efe ea kantle ka hona ha e khethoe feela ke thepa ea khothalletso eo empa hape le boemo ba ts'ebetso ea boko. Ka hona, ho bontšitsoe hore tšebetso ea Cortical ea basement e beha qeto ea hore na TMS e sitisa kapa boitšoaro ba potlakile (Silvanto et al., 2008). Molao-motheo oa ts'ehetso ea mmuso o hlalositsoeng ka holimo o tla sebetsa le ho boemo ba tsamaiso ea DA. The hypodopaminergic state (Melis et al., 2005) e lokela ho "eketsa" litlamorao tsa TMS ha e bapisoa le e lebelletsoeng tsamaisong ea DA e sebetsang.

Karabelo ea ts'ebetso ea methapo (s) ho ts'usumetso ea motlakase le synaptic e itšetlehile haholo ka likarolo tsa eona tsa morphological, tseo ka tsona li fetotsoeng haholo ke lithethefatsi tsa tlhekefetso (Robinson le Kolb, 2004) le ho ikhula kalafong e sa foleng le li-opiates (Sklair-Tavron et al., 1996; Spiga et al., 2003, 2005), cannabis derivatives / analog (Spiga et al., 2010), le psychostimulants (Robinson le Kolb, 1997) li bontšitsoe ho hlahisa liphokotso ka boholo ba lisele tsa DA (Sklair-Tavron et al., 1996; Spiga et al., 2003), e bapisoang le ho phehella (Diana et al., 2006) mekhoa e fetotsoeng ea khokahano ea synaptic, le methapo ea methapo ho Nacc le Pfcx (Robinson le Kolb, 1997). Liphetoho tsena tsa kaho li ka lebelloa ho fetola mohato o sa bonahaleng oa ts'ebetso o ka hlahisang bokhoni le karabelo ea sistimi mohopolong oa TMS. Ka hona, tlhahlobo ea netefatso ea 'nete (Spiga et al., 2010) ea likhoto tse itšetlehileng ka li-cannabis, tse hlahisoang ke ho kenya thepa ea netefalitsoeng ea morphometrical le electrophysiological, e bolela esale pele khato e ka fokotsang ts'ebetso ea nalane e tlase ea Nacc medium spiny neuron (MSN). Liphetho tsena li bontša hore MSN, ea likhoto tse itšetlehileng ka cannabis ka mokhoa o ts'oanang e na le kelello. Ho nka hore ts'ebetso e kholo ea li-neuron tsena ke glutamate ea cortical (Glu; bona puisano ho Spiga et al., 2010, le litšupiso tse ho eona; Kalivas le Hu, 2006) e hlahisa monyetla oa phokotso ea Glu joalo ka sesosa sa lebaka. Ho fumana hona, ka hona ho fana ka monyetla o mong oa hore ho hlohlelletsa likarolo tsena ka TMS ho ka ba molemo ho tsosoloseng ts'ebetso ea 'mele ea pele ho lithethefatsi. Kannete, ts'ebeliso ea cortical ea TMS e lokela ho eketsa ts'ebetso ea li-fiber tsa cortico-fugal tse nang le glutamate tse kenang lihloohong tsa mokokotlo oa Nacc MSN (Groenewegen et al., 1991). Ha re nahana ka karolo ea mantlha eo Glu e e bapalang ho polasetiki ea synaptic (Russo et al., 2010), karolo ea eona e kanna ea sebelisoa hampe ho li-paramente tsa khothaletso tsa LTP, qetellong li reretsoe ho hlahisa tsosoloso e tšoarellang le e sa feleng ea tšebetso ea 'mele ea mantlha. Litšobotsi tsena li tlameha ho tsotelloa le ho kenngoa ka mokhoa o kopanetsoeng molemong oa ho fumana li-paramethara tse nepahetseng. Ka vivo lirekoto tsa VTA-projeke ea DLPfcx neurons li thunya hanghang ho potoloha 4-6Hz (Pistis et al., 2001) le maqhubu a susumetsang a TMS a 10Hz e ka ba frequency e loketseng ho fumana keketseho e kholo ea li-neuron tse sebelisang VTA tse etselitsoeng ho khothaletsa "haelloang ” sisteme ea dopamine le molekane oa eona oa post-synaptic (ke hore, MSN ea Nacc).

Taba e 'ngoe e lokelang ho tsotelloa ke hore lithuto tsohle tse fetileng (bona kaholimo) li sebelisitse khothalletso ea TMS monolaterally, leha ho le joalo li fumana phokotso ea takatso ea joala (Mishra et al., 2010). Leha tšebeliso ea joala e sa lekanyetsoa, ​​'me litlamorao tsa tumellano e ke ke ea qheleloa ka thoko a priori, ho ka etsahala hore ts'ebeliso ea TMS ka bobeli, joalo ka H-coil (Feil and Zangen, 2010), e ne e tla fana ka ts'ebetso e matla ea cortical (palo e kholo ea likhoele e kenngoe) ka keketseho e kholo ea keketseho e kholo ea tokollo e kopaneng ea DA. Ho lokela ho hopoloa hore kopo ea unilateral TMS e se e tlalehiloe hore e tla eketsa tokollo ea DA (Strafella et al., 2001) ka mokhoa o ts'oanang ho striatum ea motho, le literekeng (Keck et al., 2002; Zangen le Hyodo, 2002), le esita le litlelong tse tlositsoeng ke morphine (Erhardt et al., 2004), ka hona, re tšehetsa motheo o hlalositsoeng kaholimo. Le ha Strafella et al. (2001) tlhahiso e khothalletsoang ea (li-Glu-tse) tsa cortico-fugal fiber tse etsang kamano ea synaptic le liteishene tse nang le li-DA maemong a ventral striatum, ho hlalosa liphetho tsa bona, ho lokela ho hlokomeloa hore ho ba teng ha mabitso axe-axonic ho lula ho botsoa ka lipotso mabapi le khaello ea lipatlisiso tse nepahetseng tsa anatomical (Groenewegen et al., 1991; Meredith et al., 2008).

Le ha lintlha tse ngata tsa tekheniki bakeng sa litekanyetso tse nepahetseng tsa ts'usumetso li hloka tlhahlobo e tsoelang pele le ts'ebetso, TMS e bonahala e lokeloa ke tlhahlobo e hlokolosi joalo ka sesebelisoa se ka bang teng kalafong ho batho ba lemaletseng joala le lithethefatsi tse ling. Ehlile, ka litlamorao tsa eona tse batlang li le sieo tsa litlamorao, litla-morao tse fokolang, le ho hlaseloa habonolo, TMS e ka fana ka monyetla oa pele oa sesebelisoa se sebetsang, se sa phekoloeng litabeng tsa bongaka, le litlamorao tse ling tsa lik'hemik'hale. Haeba e kopantsoe hantle le tumellano e tiileng ea methapo ea kutlo (DA), e ka fana ka monyetla o ikhethang oa ho ntšetsa pele "electrophysiological ” ho ithuta le ho qetella ho phekola lefu le bohloko le atileng la bokhoba.

Tlhōlisano ea Tlhaloso

Sengoli se phatlalatsa hore lipatlisiso li entsoe kamora ho se be le kamano efe kapa efe ea khoebo kapa ea lichelete e ka nkuoang e le khohlano e ka bang teng ea phaello.

lumela hore baa fokola

Mosebetsi ona o ile oa tšehetsoa ka karolo ea lichelete ke MIUR (PRIN. N ° 2004052392) le Digartimento Politiche Antidroga. Sengoli se lakatsa ho leboha S. Spiga ka ho hlakisa boitsebiso ba litšoantšo bo hlahisitsoeng.

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