Lithethefatsi le Tlhaloso (2010)

Thomas J. Gould, Ph.D.

Likarolo tsa boko le tšebetso ea maqhubu a tlasa temallo li ata haholo le tse tšehetsang mesebetsi ea kelello, ho kenyelletsa ho ithuta, ho hopola le ho beha mabaka. Ts'ebetso ea lithethefatsi libakeng tsena le lits'ebetsong nakong ea tlhekefetso ea pele e hlekefetsa likamano tse matla pakeng tsa ts'ebeliso ea lithethefatsi le tšusumetso ea tikoloho e ka bakang litakatso tsa bokamoso le boits'oaro bo batlang lithethefatsi. Ka tšebeliso e mpe ea lithethefatsi, khaello ea kelello e etsa hore ho mpefatse bothata le ho feta ba ho thibela boitšoaro. Boko bo ntseng bo hola bo angoa ka ho khetheha ke litlamorao tsa lithethefatsi tsa tlhekefetso; ho pepesetsoa bongoaneng, bongoaneng le ho ba lilemong tsa bocha li hlahisa liphetoho tse telele molemong oa kelello. Bakuli ba nang le bokuli ba kelello ba kotsing e kholo ea tlhekefetso ea lithethefatsi, 'me tšusumetso e mpe ea ho hlaphoheloa kelellong e kanna ea mpefatsa le ho feta mathata a kelello a amanang le mathata a bona a kelello.

Tlhahiso ea Mekhatlo e amanang le lithethefatsi

Mokhoa o mongata oa ho lemalla o lematsa likarabo tse matla tsa batho litabeng tsa lithethefatsi ts'ebetsong ea ho ithuta e kenyelletsang mekhatlo e matla ea tšusumetso ea lithethefatsi (mohlala, Robinson le Berridge, 2000). Ka maikutlo ana, motho ea noang moriana o lemoha tikoloho ea hae ea morao-rao e le ntho ea bohlokoa haholo (e ikhethang) mme o etsa kamano e matla lipakeng tsa likarolo tsa tikoloho eo le thabo e kholo ea moriana. Kamora moo, ha a kopana le litšobotsi tseo hape, mekhatlo e matla e ea its'oarella, ka letsoalo le tlase, mme e ba boiphihlelo joalo ka sepheo sa ho batla lithethefatsi le ho ts'oara lithethefatsi. Tumellanong le ak'haonte ena, ho pepesa batho ba lemaletseng lithahasello tse amanang le tlhekefetso ea lithethefatsi, hammoho le karabelo ea 'mele le litakatso tsa lithethefatsi, liphetoho maemong a bokong a karolo ea ho ithuta le ho hopola (mohlala, striatum, amygdala, orbitofrontal cortex, hippocampus , thalamus, le ho tloha ka letsohong le letšehali) (Franklin et al., 2007; Volkow et al., 2006).

Litlamorao tse mpe tsa amphetamine, nikotine, le koae li tšoana hantle le boemo bona. E 'ngoe le e' ngoe ea lithethefatsi tsena e bontšitsoe ho ntlafatsa haholo ho ithuta le / kapa tlhokomelo (Del et al., 2007; Kenney le Gould, 2008; Mattay, 1996). Mohlala, mohopolo oa hore ho tsuba ke tšusumetso ea kelello o amoheloa hantle ke bafuputsi le sechaba ka kakaretso. Boithuto bo bongata bo netefalitse hore mekhoa ea ho lemoha ea liphoofolo e sebetsang e ntlafatsa kapele kamora ho tsamaisoa ha nicotine (Kenney le Gould, 2008). Liphumano tse tšoanang liphuputsong tsa pele le batho ba tsubang ha lia ka tsa boleloa, hobane barupeluoa ba ne ba tsubile ba neng ba amohetse nikotine kamora nako ea ho khaotsa ho tsuba. Lintlafatso tse bonoang li kanna tsa bonts'a phetoho ea litlamorao tsa ho tlohela, ho e-na le ntlafatso holim'a matla a bona a tloaelehileng a ho lemoha. Tlhahlobo e ileng ea latela ea lingoliloeng, leha ho le joalo, e fana ka maikutlo a hore nicotine e bohloko haholo e ntlafatsa nako ea karabelo le tlhokomelo ho batho ba nicotine-naïve (Swan le Lessov-Schlaggar, 2007). Cocaine e hlahisitse litlamorao tse tšoanang thutong ea likhoto tse phekotsoeng ka moriana oo ebe li fuoa tšusumetso ea maikutlo; liphoofolo li bontšitse ts'ebetso e ntlafalitsoeng ea neural ha hamorao e hlahella hape ho khothalletso (Devonshire, Mayhew, le Overton, 2007).

Le ha lithethefatsi tsohle tsa tlhekefetso li hlohlelletsa thuto ea litloaelano tse matla tsa khothalletso ea lithethefatsi le ho ts'oara lithethefatsi tse khothalletsoang, tse ling li bonahala li na le litlamorao tse fapaneng mefuteng e meng ea ho ithuta le ho amohela. Mohlala, boithuto ba bongaka ba litlamorao tse mpe tsa morphine le oxycodone li fihletse qeto ea hore lithethefatsi tsena li na le litlamorao tse fetoleng tlhokomelong ea batho: Bobeli bo ntlafalitse khopotso ea banna ka prose hanyane hanyane, empa morphine e sentse ts'ebetso ea ba batona ba batšehali tekong ea mohopolo o sebetsang oo ba o sebelisang. ba ile ba kopuoa ho pheta palo ea linomoro ka tatellano e fapaneng (Friswell et al., 2008). Phuputsong e 'ngoe, litoeba li ile tsa fuoa morphine kapa saline' me tsa koetlisetsoa ho baleha ha leseli le ne le supa hore ho na le leqhubu la maoto le emang; leha litoeba tse tšoeroeng ke morphine li ipabola holima khafetsa le ka potlako moo ba qobang ho makala, bafuputsi ba re sena se ekelitse ts'ebetso ea makoloi ho fapana le ho ithuta ka mokhoa o ntlafatsang (Aguilar, Miñarro, le Simón, 1998). Ho fapana le litlamorao tsa li-opioid ho cognition, tseo tsa joala li hlakile, leha ho le joalo, li fana ka maikutlo a hore: Meli e phahameng e sitisa mekhoa ea kutloisiso (Ryback, 1971), ha litekanyetso li tlase li ka ntlafatsa ho ithuta (Gulick le Gould, 2007; Hernández, Valentine, le Powell, 1986).

Kholiseho ea Mekhatlo e Mebetsang ea Lithethefatsi

Patlisiso ea morao tjena e batlile ho ikarabella bakeng sa bokhoni ba nako e telele bo makatsang ba mekhatlo e khothalletsang lithethefatsi ho susumetsa boitšoaro le ho baka ho oela hape. Boithuto bo bonts'itse hore lintho tse ngata tse hlekefelitsoeng li ka fetola mekhoa ea puisano lipakeng tsa li-neuron (synaptic plasticity), tse ka tlatsetsang ho theheng le phehelong ea mekhatlo e khothalletsang lithethefatsi hampe.

Cocaine le nicotine li ka lebisa ka kotloloho mofuta o le mong oa polasetiki ea synaptic, ho matlafatsoa ha likhokahano tsa neural ka ts'ebetso e tsejoang ka hore ke tšebeliso ea nako e telele (LTP; bona ho Ithuta Mohopolong le Brain leqepheng la 8 le Lethathamo 1) (Argilli et al., 2008; Kenney le Gould, 2008). Amphetamine e ka ntlafatsa LTP (Delanoy, Tucci, le Khauta, 1983). Marijuana e kenya ts'ebetsong tsamaiso ea endocannabinoid, e lebisang ho sitisang maemong a mang le ho nolofalletsa ho ba bang ba bobeli ba LTP le khatello ea maikutlo ea nako e telele (LTD), mofuta o mong oa polasetiki ea synaptic moo likhokahano pakeng tsa li-neurons li sa arabeleng habonolo (Carlson, Wang, le Alger, 2002; Nugent le Kauer, 2008; Sullivan, 2000). Ethanol e lula e sitisa LTP ha e ntse e ntlafatsa LTD (Yin et al., 2007). Morphine inhibits LTP ea li-neuron tse bontšang taolo ea thibelo ea tšebetso ea neural ka neurotransmitter gamma-aminobutyric acid (GABA) (Nugent le Kauer, 2008). Ho thibela ts'ebetso ea GABA ho ka lebisa keketseho e akaretsang ea tšebetso ea methapo ho ea bokong, tse ka lebisang ho thehoeng ha likamano tse matla ho feta tse neng li tla etsahala hangata, ho kenyelletsa le litloaelano tse mpe tsa lithethefatsi.

  

TABLE 1

Liphello tsa lithethefatsi ho Plnity ea Synaptic

Ho matlafatsa bopaki ba hore lithethefatsi li khothaletsa mekhatlo ea nako e telele ea ts'usumetso ea lithethefatsi ka ho ama polasetiki ea synaptic, liphuputso li bontšitse hore liprotheine tse tšoanang tse nkang karolo ho latellaneng hoa biochemical reaction (cell signaling Cascades) tse laolang synaptic plasticity (bona Setšoantšo sa 1) kenella mekhoeng ea boitšoaro bo batlang lithethefatsi. Mohlala, tekong e 'ngoe, bafuputsi ba bontšitse hore ha likhoto li ea sebakeng sa likhomo tseo ba neng ba koetliselitsoe ho li kopanya le koae, maemo a liprotheine tse amanang le ho ithuta — extracellular sign-regated protein kinase (ERK), cyclic AMP reaction element- binding (CREB), Elk-1, le Fos-li eketsehile ka NAc ea tsona (Miller le Marshall, 2005). Ho feta moo, ha likhoto li tšoaroa ka komporo e hatellang ERK, ba emisa ho khetha sebaka seo sa likhopo ho feta se le seng moo ba amohetseng saline mme ba supa ho fokotseha ha barupeluoa ba bararo ba biochemical ho LTP (CREB, Elk-1, le Fos) ho NAc.

  

Tšoantšiso 1

Cascade e Botsang Cell ho Ithuta le ho Hopola

Lits'oants'o tsa Bokhachane

Litlamorao tsa ho pepesetsoa joala ka prenatal li tsejoa hantle: Mathata a bonoang ke "fetal alcohol" ke sesosa se ka sehloohong sa ho khutlisetsoa kelellong United States (Litsi tsa Taolo ea Thibelo ea Maloetse le Thibelo ea Maloetse, 2009). Ntle le moo, ho pepesetsoa joala ba fetana ho eketsa mathata a tlhekefetso ea tlhekefetso ea moraorao (Yates et al., 1998).

Ho pepesetsoa bokhachane ho lingaka tse ling tse 'maloa ho na le litlamorao tse mpe tsa kelello le boits'oaro bo ka' nang ba se ke ba nyoloha boemong ba ho khutla kelellong. Phuputsong e 'ngoe, bana ba lilemo li 5 bao bo-'m'a bona ba neng ba sebelisitse joala, koae le / kapa li-opiates ha ba le moimana ba behiloe ka tlase tlasa taolo e sa senoloang lithutong tsa puo, taolo ea tšusumetso, le tlhokomelo ea pono. Ho ne ho se na phapang e kholo lipakeng tsa lihlopha tse peli tsa bana ka bohlale, pono / tataiso ea tataiso, kapa tlhokomelo e tsitsitseng; leha ho le joalo, lihlopha tsena ka bobeli li kentse ka tlase ho mokhoa o tloaelehileng mehatong ena (Pulsifer et al., 2008). Phuputso e 'ngoe e tlalehileng liphokojoe tsa ho hopola bana ba 10 ea lilemo li' nileng ba pepesetsoa joala kapa matekoane bohlasoaRichardson et al., 2002).

Phuputso ea tliliniki le ea laboratori e thatafalitse ho pepesetsoa ha methamphetamine litla-morao tsa kelello le bofokoli ba sebopeho sa boko. Mohlala, phuputso e le 'ngoe e kopantseng nako e khuts'oane ea tlhokomelo mme e liehisa mohopolo ka molumo o fokotsehileng ho putamen (karolo ea −18), globus pallidus (−27 ho −30 lekholong), le hippocampus (−19 ho −20 lekholong) ho bana ba 15 ba lilemo li 3 ho lilemo tsa 16 ba neng ba pepesetsoa prenatally ka pherekano, bapisoa le taolo (Chang le al., 2004). Bana ba pepesetsoeng lithethefatsi ba boetse ba bonts'a memori e telele ea mafutsana ea nako e telele le kopanyo ea pono / koloi. Phuputso e ngoe e ngotse liphetoho tsa sebopeho ka pele le parietal cortex ea bana ba 3- le 4 ea lilemo li ileng ba pepesetsoa methapo ea methapo bakeng sa methamphetamine (Cloak et al., 2009). Lithutong tsa laboratori, likhoto tse neng li tšoaroa ka methamphetamine nakong ea kemolo li ile tsa tsoala malinyane ao, ha a fihla lilemong tsa ho ba motho e moholo, a lieha ho ithuta likamano tsa moea mme a bonts'a tšenyo ea sebaka sa mohala (Acuff-Smith et al., 1996; Slamberová et al., 2005).

Litlamorao tsa ho pepesetsoa koae ea batsoetse ho tsuba li bohlokoa haholo hobane bo-mme ba bangata ba lebelletseng ho tsuba — ka khakanyo e le 'ngoe, liperesente tse 10 tsa United States (Hamilton et al., 2007). Ho uena ho pepesetsoa litšibollo tsa koae ho hokahanngoa le bofokoli ba kelello ba liphoofolo le tsa bana ba lilemong tsa bocha ((Bacha ba lilemong tsa bocha)Dwyer, Broide, le Leslie, 2008). Liphuputso tse ling li bontša hore ho pepesetsoa joalo ho ka fokotsa bohlale ba kakaretso; mohlala, e mong o fumane lekhalo la lintlha tsa 12 ho IQ e akaretsang lipakeng tsa bacha ba lilemong tsa bohareng tse sa senoloang (mohlala, Fried, Watkinson, and Grey, 2003). Phuputsong e 'ngoe, menyetla ea ho ba le bothata ba ho fokola ka lebaka la tlhaselo ea kelello (ADHD) e ne e le makhetlo a fetang a mararo ho bacha bao bo-mme ba bona ba neng ba tsuba nakong ea kemolo ha ba bapisoa le bana ba bo-mme ba sa tsubeng.Pauly le Slotkin, 2008).

Khaello ea kelello ka mor'a ho pepesetsoa ho tsuba e ka bonts'a liphetoho tsa bokong. Phuputsong e 'ngoe, batho ba tsubang ba lilemong tsa bocha ba tsubang ba ne ba e-na le bofokoli bo boholo ba pono ea ho bonana hammoho le liphetoho mesebetsing ea parahippocampal le hippocampal ha e bapisoa le batho ba tsubang ba sa tsubang lilemong tsa bocha.Jacobsen et al., 2006). Menahano ea kelello ea batho ba tsubang ea lilemong tsa bocha le ba sa tsubeng ba neng ba pepesetsoa ho tsuba e senotse ho fokola ha (cortical unness)Toro et al., 2008le liphetoho tse hlophiloeng molemong oa taba e tšoeu ea cortical (Jacobsen et al., 2007). Ntle le moo, ho litoeba, ho pepesetsoa bokhachane ho nicotine ho fokotse tšebetso e amanang le memori hippocampus mme ho fella ka bofokoli ba ho ithuta ka tieo ho ithuta, ka litoeba tsa banna le tsa basali tse pepesitsoeng tse bontšang karabo tse sa nepahalang haholo joaloka batho ba baholo ba banyenyane (Vaglenova et al., 2008). Liphoso tsena li ile tsa tsoela pele ho ba batho ba baholo hamorao har'a litoeba tse tona, empa eseng tse tšehali.

Har'a tse bohloko tse tlisoang ke ho pepesetsoa lithethefatsi bongoaneng ke kotsi e kholo ea ho ba lekhoba la lithethefatsi bophelong ba kamoso (Fergusson, Woodward, le Horwood, 1998). Sena sea khathatseha, kaha se ka lebisa khaellong e tlase e bonahatsang meloko le ho senya malapa. Ho na le mabaka a mangata a ka bakang kotsi e kholo ea tlhekefetso ea lithethefatsi nakong e tlang, ho kenyelletsa le litlamorao tsa ho pepesetsoa lithethefatsi bongoaneng. Joalokaha ho se ho hlahlojoa, kotsi ea ho ba le ADHD e eketseha haholo ho bacha bao bo-mme ba bona ba neng ba tsuba nakong ea kemolo (Pauly le Slotkin, 2008). Hangata ADHD e bapisoa le tlhekefetso ea lithethefatsi (Biederman et al., 2008; Molina le Pelham, 2003), ho fana ka tlhahiso ea khokahano lipakeng tsa liphetoho tse joalo temohong le tšebeliso e mpe ea lithethefatsi. Ho hlokahala mosebetsi o eketsehileng ho utloisisa mekhoa e tlisoang ke kotsi ea tlhekefetso ea lithethefatsi e amanang le ho pepesetsoa masea.

Phatlalatso ea Bacha

Bocha ke nako e kotsing e kholo ea tlhekefetso ea lithethefatsi. Boholo ba batho ba tsubang ba ile ba qala ho itloaetsa bona nakong ea bohlankana.Khuder, Dayal, le Mutgi, 1999). Ho tsuba ba lilemong tsa bocha ho ama motho ka matla. Bacha ba tsubang ba fumane liphoso tse mpe ho feta tsa batho ba sa tsubeng lilemong litekong tsa mohopolo o sebetsang, kutloisiso ea mantsoe, ho bala ka molomo le ho hopola lintho ka hlooho (Fried, Watkinson, and Grey, 2006; Jacobsen et al., 2005). Liphoso tsena li ile tsa rarolloa ka mor'a ho khaotsa ho tsuba ntle le ho lebala ka ho sebetsa le ho bala ka lipalo, tse ileng tsa sala li le tlase haholo. Litekong, ho pepesetsoa ha nikotine nakong ea bohlankana ho ne ho amana le bofokoli ba tlhokomelo ea pono, ho eketseha ha maikutlo, le ho eketseha ha maikutlo a litokelo tsa kalafo tsa dopamine tsa kalafo ea methapo.Counotte et al., 2009). Ntle le moo, likhoto tsa bocha tse tšoeroeng ke nicotine li bile le liphetoho tsa nako e telele kutloisisong ea seleng ea adenylyl cyclase cell signaling Setšoantšo sa 1), tsela ea len messengerosa la bobeli e kenelletseng lits'ebetsong tse ngata, ho kenyelletsa ho ithuta le ho hopola (Slotkin et al., 2008). Liphumano tsena li lumellana hantle le liphuputso tse bonts'ang hore nicotine qalong e ka ntlafatsa lits'ebetso tse ling tsa kelello, empa ka ts'ebeliso e tsitsitseng ea ts'ebeliso e ka hlaha, e lebisang ho ho felisoa ha litlamorao tsena esita le bofokoli (bakeng sa ho hlahloba, bona Kenney le Gould, 2008).

Ho tsuba ba lilemong tsa bocha ho ka holisa ho akheha ha kelello ka mokhoa o sa tobang, ka ho phahamisa mafu a mang. Mohlala, ts'ebeliso ea koae ea bongoana e amana le liketsahalo tsa khatello ea maikutlo hamorao (Choi et al., 1997), lefu le amanang le lona le amahanngoa le litlamorao tse mpe tsa kelelloThomas le O'Brien, 2008). Patlisiso ea laboratori e hlakisa kamano ena: Likhoto tsa batho ba baholo tse neng li pepesehetse nicotine nakong ea bocha ba bonahetse li le bohlasoa haholo ho feta taolo ea litheko tse khothatsang le takatso e matla ea khatello ea maikutlo le khatello ea kelello (Iñiguez et al., 2009).

Ho pepesetsoa lintho tsa bongoaneng linthong tse ling tsa tlhekefetso, joalo ka joala, cannabis le MDMA, le tsona li baka pherekano e sa feleng ea temohisiso (Brown et al., 2000; O'Shea, McGregor, le Mallet, 2006; Piper le Meyer, 2004; Stiglick le Kalant, 1982). Liphumano tsena li bonts'a hore boko ba bongoana, bo ntseng bo tsoela pele ho ts'oaroa, bo ka tšosoa ke tšebeliso ea lithethefatsi le tlhekefetso, 'me ho nyefola ho joalo ho ka baka liphetoho tse tšoarellang tse amang le ho hlokofatsa.

Kelello ea ithuta: E nka le ho boloka tlhaiso-leseling le ho bonts'a likamano lipakeng tsa bona. Bakeng sa kelello ho ithuta, liketsahalo li tlameha ho etsahala bokong. Har'a lintho tse fanang ka bopaki bo matla haholo bakeng sa mohopolo ona ho na le batho ba bangata ba ileng ba fokotseha haholo ke bokhoni ba bona ba ho ithuta kamora ho lemala ha boko. Mohlomong ea tummeng ka ho fetesisa ke Henry Molaison, eo kamora ho etsoa opereishene ea ho tlosa manonyeletso a mangata a bongoaneng 27 ho laola lefu la sethoathoa, a ileng a lahleheloa ke mohopolo oa nako e telele oa ho hlaka (1).Penfield le Milner, 1958) e le hore ka lilemo tse setseng tsa 55 tsa bophelo ba hae o ne a sa khone ho hopola letho le mo etsahaletseng ho feta metsotso e mmaloa pejana.

Patlisiso ea Neuroscience e hokahantse thuto le ntlafatso ea li-network tsa neural bokong. Liteko tse ngata li fumane hore, ha ho ithuta ho etsahala, li-neuron tse khethiloeng li eketsa maemo a tsona a tšebetso 'me li theha likhokahano tse ncha, kapa li tiisa likhokahano tse tsitsitseng, ka li-network tsa li-neurons tse ling. Ho feta moo, mekhoa ea liteko e thibelang ts'ebetso ea neuronal le marang-rang a thibelang ho ithuta.

Patlisiso ea Neuroscience le liphoofolo e hlakisa hore na kelello e theha le ho boloka li-network tsa neural tse tšehetsang ho ithuta joang. Ts'ebetso e le 'ngoe e anngoeng, ea nako e telele ea ts'ebetso (LTP), e na le likarolo tse lumellanang likarolo tsa bohlokoa tsa ho ithuta.

• Ha re ithuta ho hokahanya mehopolo kapa maikutlo a mabeli, ho ba teng ha e 'ngoe ho ka etsa hore re hopole e' ngoe. Ka mokhoa o ts'oanang, ho PDP, neuron e fumanang matla a matla, kapa maqhubu a phahameng, e tsoang ho neuron e 'ngoe e arabela ka ho ba le hloko haholoanyane ho ho hlohlona nakong e tlang ho tsoa mohloling o le mong;
• Lintho tse sa tsoa ithuta li kena mohopolong oa rona oa nako e khuts'oane 'me li ka' na tsa se ke tsa hlola tsa hopola nako e telele. Ka mokhoa o ts'oanang, LTP e na le mohato oa pele nakong eo ts'ebetso ea nakoana ea boikoetliso ba 'mele e tšehetsang keketseho e boletsoeng ka holimo ea methapo ea kutlo ea methapo le karolo ea morao e kenyeletsang lits'ebetso tsa mmele tse tšoarellang nako e telele;
• Lithuto tsa liphoofolo li ts'oaretse tse ling tsa tatellano e tšoanang ea liphetoho tsa biochemical (cell signaling cascades) ho LTP le ho ithuta. Mohlala, bafuputsi ba bonts'itse hore ho hatella tlhahiso ea enzyme (protheine kinase A) hippocampi ea litoeba e thibetse LTP mme ea sitisa bokhoni ba liphoofolo ba ho boloka leseli le ithutileng ka maze (Abel et al., 1997).

Le ha PDP e sa ka ea bonoa sebakeng se seng le se seng sa boko, e bontšitsoe ka har'a li-nucleus bokell, cortex ea pele, hippocampus le amygdala - libaka tsohle tse kenyelletsang ho lemeng le ho ithuteng (Kenney le Gould, 2008; Kombian le Malenka, 1994; Maren, 2005; Otani et al., 2003).

Sebopeho sa liphatsa tsa lefutso tsa motho e mong se ka susumetsa hore na lithethefatsi tsa tlhekefetso li fetola mekhoa ea hae ea kutlo. Mohlala, karabelo ea motho ea kelello ho amphetamine e matla e itšetlehile ka hore na ke mefuta efe e meng ea Catechol-O-methyltransferase (COMT) mofuta oo a o futsitseng.

Mofuta ona o kenya protheine e sebetsang ka har'a dopamine le norepinephrine, har'a limolek'hule tse ling. Motho o rua likopi tse peli tsa mofuta, e 'ngoe ho motsoali e mong le e mong,' me kopi ka 'ngoe e na le "valine" kapa "methionine" "" "" "" "codon 158: ka hona motho a ka ba le valine e' ngoe (Val / Val), methionine e 'meli (Met / Met ), kapa para e kopaneng (Val / Met kapa Met / Val) ea li-codon sebakeng sena. Tsamaiso ea amphetamine e matla ho batho ba nang le boleng ba boleng ba Val / Val e ntlafalitse ts'ebetso ea bona ho Wisconsin Card Sorting Task (tlhahlobo ea ho tenyetseha hoa kelello e etsang hore ts'ebetso ea cortex ea dorsolateral e be teng pele le ts'ebetso e kholo mosebetsing oa bona oa pele oa cortical, joalo ka ha o lekantsoe ke ho eketseha ha mali a likhoerekhoere. phallela lebopong le ka tlase la lobe (Mattay et al., 2003). Leha ho le joalo, acphe amphetamine ha ea ka ea hlahisa melemo eo ho batho ka bomong ba nang le Val / Met kapa Met / Met pa Met. Ho khahlisang, boleng ba boleng ba Val / Val bo boetse bo amahanngoa le ho ba le khatello e eketsehileng, tšobotsi e amanang le bokhoba ba tahi (Boettiger et al., 2007).

Ntle le moo, batho ba tsubang ba nang le boleng ba Val / Val ba ne ba amehile haholo ka litlamorao tse mpe tsa ho tlohela ha nicotine molemong oa ho sebetsa mme ba bonts'a karabelo e kholo ea kelello ea ho tsuba (Loughead et al., 2009). Liphetho tsena ha li bohlokoa hobane feela li bontša khokahano lipakeng tsa litlamorao tsa lithethefatsi tsa tlhekefetso ho boiphihlelo le litloaelo tsa boits'oaro, empa hape hobane li fana ka mehlala ea hore na genotype e kenya letsoho joang ho ts'ebelisong ea litekanyetso.

Sengoli se rata ho leboha Dr. Sheree Logue le litho tsa Gould Laborator bakeng sa ho bala ka mokhoa o hlakileng tlhahlobo ea pejana le ho amohela tšehetso ea lithuso ho tsoa ho National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, le National Cancer Institute (AA015515, DA017949, DA024787, le P50 CA143187) bakeng sa tse ling tsa lithuto tse lekiloeng.

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