Ho khannoa ka matla le ho se na brake: ho ba le khatello ea kelello ea tsoelo-pele le kotsing ea ho sebelisa lithethefatsi hampe (2009)

Neurosci Biobehav Rev. 2009 Apr;33(4):516-24.

Andersen SL, Teicher MH.

mohloli o moholo

Lenaneo la Patlisiso ea Biopsychiatry e ntlafalitsoeng, Sepetlele sa McLean / Sekolo sa Bongaka sa Harvard, Belmont, MA 02478, USA. [imeile e sirelelitsoe]

inahaneloang

Liketsahalo tse fapaneng tsa bophelo li amahanngoa le mefuta e mengata ea psychopathology, ho kenyelletsa le kotsi e eketsehileng ea tlhekefetso ea lithethefatsi. Thutong ena, re tsepamisa likamano lipakeng tsa ho pepesetsoa litsietsing le kholisong ea boko, 'me re amahanya sena le liwindows tse ntlafalitsoeng tsa tlokotsing. Tlhahlobo ena e akaretsa lintlha tsa tliliniki le tsa tlhahlobo ea pele, bopaki bo tsoang lipatlisisong tsa lefu lena, lithuto tsa ho nahana ka morphometric le tse sebetsang, le biology ea limolek'hule le genetics. Tšebelisano ea ho pepeseha nakong ea linako tse mahlonoko le liketsahalong tsa kholo e hlahisa mofets'e o lebisang ho qalisong ea ts'ebeliso ea lithethefatsi lilemong tse nyane, mme e eketsa monyetla oa tšebeliso ea bokhoba ke bohlankana kapa boroetsana. Mofuta oa khatello ea maikutlo ea ho imeloa kelellong / corticolimbic o khothalletsoa ho latela lipapatso tsa khatello ea maikutlo, sethala sa nts'etsopele, le liketsahalo tsa neuromaturational tse ka hlalosang ho batla ha lihlopha tse ikhethang tsa lithethefatsi hamorao bophelong. Lintho tse tharo tsa mantlha li kenya letsoho kholisong ena ea lilemo tsa ts'ebeliso ea lithethefatsi e tsoetseng pele: (1) sistimi e arabelang khatello ea maikutlo; (2) linako tse mahlonoko tsa ho ba kotsing; le (3) mekhoa ea boithuto nakong ea bohlankana. Ka bobeli, lintlha tsena li ka hlalosa hore na hobaneng ho pepeseha litsietsing tsa pele ho eketsa kotsi ea ho sebelisa lintho tse hlekefetsang nakong ea bocha.

Keywords: tlhekefetso, bohlankana, joala, cocaine, nako e hlokofatsang, e susumetsang, khatello ea maikutlo

Eya ho:

Selelekela

Mathata a bongoana a bakoang ke tlhekefetso, tahlehelo ea motsoali, bopaki ba tlhekefetso ea malapeng kapa ho hloka taolo ea lapeng ke sesosa se seholo sa bophelo bo botle ba kelello le ba mmele (Chapman et al., 2004; Dube et al., 2003; Felitti, 2002). Phello e 'ngoe e kholo ea mahlomola a pele ke kotsi e kholo ea ts'ebeliso ea lithethefatsi, tlhekefetso le boikemelo (Dube et al., 2003). Rona, le ba bang, re khothalelitse hore tlhekefetso ea bongoana e hlahise liketsahalo tse ngata tsa liketsahalo tsa 'mele le tsa tlhaho tse fetolang likarolo tsa kholo ea kholo (mohlala, (Andersen, 2003; Teicher et al., 2002)) le hore litlamorao tsa ho pepesetsoa tlhekefetso ea bongoana li ts'oana le litlamorao tsa ho pepesetsoa khatello ea kholo lithutong tsa pele (Teicher et al., 2006). Morero oa tlhahlobo ena ke ho akaretsa tse ling tsa litlamorao tsa khatello ea mantlha mabapi le nts'etsopele ea boko ho liphoofolo le batho, tse shebanang le litloaelano tse ka thusang ho hlakisa khokahano ea mabaka lipakeng tsa litsietsi tsa pele le ts'ebeliso e mpe ea joala, nicotine le lithethefatsi tse seng molaong. . Khatiso e kholo ea tlhahlobo ena e tla ba lintlafatsong tsa nts'etsopele / ea nakoana, ho elelloa hore tšebeliso e mpe ea lithethefatsi ke "tlholeho e tsoelang pele" eo ho nang le ts'ebetso ea ts'ebeliso ea lithethefatsi tsa tlhekefetso e ka lebisang tlhekefetsong le ho its'etleha (Litho tsa et al., 2003; Wagner le Anthony, 2002). Moralong ona re kenyelletsa bopaki bo bocha ba ho ba teng ha linako tse mahlonoko tseo ho tsona likarolo tsa kelello tse sa bonahaleng li amehang habonolo litlamorao tsa khatello ea maikutlo, 'me re totobatsa nako e kholo ea nako e kholo e ka kenang lipakeng tsa nako ea ho pepesa le ho hlahisa liphetho tse bohloko.

Eya ho:

Epidemiology ea Tlhabollo ea Kelello le Tlhekefetso ea Lithethefatsi

Tšusumetso ea tlokotsi ea bongoana e bonts'oa ka mokhoa o hlakileng ho Tlhahlobo ea Adult Childhood Experience (ACE) e thehiloeng ho lipatlisiso tsa morao-rao tsa litho tsa 17,337 tsa Kaiser-Permanente HMO e San Diego (Chapman et al., 2004; Dube et al., 2003; Felitti, 2002). Palo ea li-'sisi tse fapaneng tsa li-ACEs 'ka ho itšetleha' e eketsa matšoao kapa ho ata ha maloetse. Kotsi e anngoeng ke baahi e amanang le litsietsi tsa pele e ne e le 50% bakeng sa ts'ebeliso e mpe ea lithethefatsi, 54% bakeng sa khatello ea maikutlo ea hona joale, 65% bakeng sa joala, 67% bakeng sa liteko tsa ho ipolaea, le 78% bakeng sa ts'ebeliso e mpe ea lithethefatsi (Chapman et al., 2004; Dube et al., 2003). Boithuto bo bong bo fuputse likamano lipakeng tsa tlhekefetso ea lithethefatsi le litsietsi tsa bana. Bosholu ba ho pepesetsoa tlhekefetso ea thobalano ea bana (CSA) le kotsi ea ts'ebeliso e mpe ea lithethefatsi le lithethefatsi li ile tsa hlahlojoa ho latela karohano ea CSA ka mekhahlelo e meraro (Fergusson et al., 1996). Ho hlophisoa ha lintlha tsa kelello, CSA e sa amaneng le eona e ne e sa amanngoe le keketseho e kholo ea menyetla ea joala kapa ts'ebeliso e mpe ea lithethefatsi / ho its'etleha. Ikopanye le CSA ntle le ho etsa thobalano le kotsi e eketsehileng ea tlhekefetso ea joala / ho lemalla, empa eseng bakeng sa ts'ebeliso e mpe ea lintho tse ling. Leha ho le joalo, CSA e kenyelletsang ho leka / ho qeta ho kopanela liphate e eketsa kotsi ea ts'ebeliso e mpe ea lino tse tahang / ho itšepa 2.7-fold le kotsi e eketsehang ea tlhekefetso ea lithethefatsi / ho ts'epahalla 6.6-fold. Kendler le basebetsi mmoho (Kendler et al., 2000) e boetse e bonts'a ho teba ha CSA ho bohlokoa, empa thutong ena esita le maemo a tlase a ne a amahanngoa le kotsi e eketsehileng. Ka bokhutšoanyane, ba fumane hore CSA eo e seng ea setho sa botona e amana le keketseho ea 2.9-fold ea menyetla ea ts'ebeliso ea lithethefatsi, athe CSA e amanang le thobalano e ne e amana le keketseho ea 5.7-foldKendler et al., 2000).

Kamano e lipakeng tsa tšoaro e mpe ea joala le joala kapa tšebeliso ea lithethefatsi e bonahala e sa le monyane haholo. E le karolo ea tlhahlobo e kholo ea sekolo sa sechaba sa bacha ba nang le boits'oaro bo botle ba bocha, baithuti ba lihlopheng tsa 8, 10, le 12 (N = 4790) ba ile ba botsoa mabapi le tšebeliso ea lithethefatsi tsa nakong e fetileng le tsa hona joale mme ba botsoa (e / che) mabapi le tšebeliso ea 'mele e fetileng le tlhekefetso ea thobalano (Bensley et al., 1999). Tlhekefetso e ne e amahanngoa le keketseho e fetang ea 3 ea mehopolo eo liteko tsa joala / tsa koae li etsahetseng ka tsona, le keketseho e fetang ea 12 ea menahanyo eo ts'ebeliso ea matekoane e sebelisoang kapa ho nooa khafetsa e bile teng ka lilemo tsa 10. Bakeng sa barui ba robeli, tlhekefetso e kopaneng ea thobalano le 'mele e ne e amahanngoa le kotsi e kholo ea 2-khanya ea khanya e fokolang le ho eketseha ha 8 ka makhetlo a mangata. Bakeng sa li-graders tsa 10th, tšoaro e mpe e ne e amahanngoa le keketseho ea 2-fold ea menyetla ea khanya e fokolang le ho eketseha ha menyetla ea 3 ka makhetlo a mangata. Leha ho le joalo, ka sehlopha sa 12th, boemo ba ho noha ba bacha ba sa tšoaroang hampe bo ne bo lekana hantle le ba tlalehileng tlhekefetso. Ho pepesetsoa mokhahlelong o mong le o mong oa mathata a bongoana ho amahanngoa le keketseho ea 2- ho ea 4-hangata menyetla ea ts'ebeliso e seng molaong ea lithethefatsi ka lilemo tsa 14 (Dube et al., 2003). Ntle le moo, CSA e imenne habeli kotsi ea tšebeliso ea lithethefatsi ea motsoali bophelo bohle, mme e eketsehile ka ho feta 12-beha menyetla ea hore tšebeliso ea lithethefatsi tsa botsoali e tla qala a sa le monyane (Holmes, 1997). Ka kopanelo, lithuto tsena li fana ka maikutlo a hore ho pepesehela khatello ea maikutlo ho tloha pele ho ntlafatsa bophelo ba kelello ka kakaretso, le phetoho ea ts'ebeliso ea lithethefatsi ho ea lilemong tse tlase. Boholo ba phello bo itšetlehile ka tekanyo ea ho pepesetsoa mefuta e fapaneng ea tlhekefetso kapa ho teba ha foromo ea mantlha. Ka lebaka leo, liperesente tse ngata tsa batho ba hlekefetsoang li senoloa nakong ea ts'ebetso ea tlokotsi ea ts'ebeliso ea ts'ebeliso ha ts'ebeliso e kanna ea lebisa tlhekefetsong le ho its'etleha nakong e tlang (King le Chassin, 2007; Orlando et al., 2004).

Likarolong tse setseng tsa tlhahlobo ena, re hlalosa mohlala o kenyelletsang nako ea ho pepesa khatello ea maikutlo e hokahana le lits'ebetso tse tloaelehileng tsa tlhabollo ho matlafatsa tlokotsi ea lintho tse hlekefetsang. Re sa tsoa fana ka tlhahiso ea papatso ea khatello ea maikutlo e emisang khatello ea maikutlo / khatello ea maikutlo (corticolimbic development Cascade) e fanang ka maikutlo a hore mathata a pele a ka 'na a amahanngoa le pontšo ea pejana ea matšoao a sithabetsang ha a bapisoa le sechaba se tloaelehileng.Andersen et al., 2008; Teicher et al., Ka khatiso). Mona, re sebelisa mohlala o tšoanang ho hlalosa hore na ho pepesetsoa khatello ea maikutlo ho tloha bonyenyaneng ho ka etsa hore motho a sebelise lithethefatsi hampe le ho feta lilemong tse tloaelehileng ho feta tse tloaelehileng bathong.

Eya ho:

Neurobiology ea Tlhekefetso ea Lithethefatsi - a haholo Moralo oa Motheo

Lithethefatsi tse nkoang li le molemo li hlahisa liphetoho tse ngata tse kenyelletsang ts'ebetsong ea bokhoba ba methati e le bohareng ba mantlha ke likarolo tse 'maloa tsa bohlokoa tsa boko (Hyman et al., 2006). Taba ea pele, maikutlo a monate, a thabisang a hokahanang le lithethefatsi tsohle tsa tlhekefetso a amahanngoa le dopamine e eketsehang ka har'a li-nucleus accumbens (Dayan le Balleine, 2002; Koob le Swerdlow, 1988; Weiss, 2005). Taba ea bobeli, hippocampus e kopanya ts'ebetso ea ho ithuta ka mokhoa ona, 'me e boloka mohopolo oa mekhatlo ea boiphihlelo (Mohau et al., 2007). Joale hippocampus e khona ho feto-fetola kapa ho araba ka "liheke" tsa li-nucleus tse bokellanang ho bonts'a liphihlelo tsena tsa pele. Taba ea boraro, likhakanyo tsa tikoloho tse amanang le boiphihlelo ba tšebeliso ea lithethefatsi li fuoa boleng bo emang ka matla ka mekhoa ea maemo (Berridge, 2007). Sesosa se susumetsang se hlahisoang se kopantsoe haholo-holo ke sepheo sa "cortex" sa boithabiso bo tlang pele ho li-accumbens (Kalivas le al., 1998; 2005; Pickens et al., 2003; Robinson le Berridge, 1993), le mekhatlo ea litlokotsebe ea lithethefatsi e thehiloeng Amygdala (Sheba le al., 2003). Ho itšetleha ka lithethefatsi ho hlaha letotong le ikhethileng la li-neuroadaptations tse etsahalang kamora tšebeliso e pheta-phetoang (Hyman et al., 2006). Litloaelo tsena li ka etsahala maemong ohle a mantlha kamora ho pepesehela lithethefatsi khafetsa. Haele hammoho, moelelo oa "ho khanna ka mokhoa o hlokang ts'ireletso" o kenyelletsa mehopolo e meraro ea hore na mahlomola a pele a ka fetolela likarolo tsa boko joang tse tsamaisang lits'ebetso tsa ts'ebetso le potoloho ka boeona (bona Setšoantšo sa 1).

Setšoantšo sa 1

Ho "tsamaisoa ka mokhoa o tenang ntle le mariki" ho bontšoa ke potoloho ena ea kelello e senotsoeng ke khatello ea kelello. Tlas'a linaha tse senang bokhoba, li-nucleus li fumana tlhahiso ho tsoa libakeng tse 'maloa tsa boko, ho kenyelletsa hippocampus le pele ho pele ...
Eya ho:

Khatello ea maikutlo / khatello ea kelello ea khatello ea maikutlo (cortication-incubation / corticolimbic)

Ho latela lingoliloeng tse hlahlojoang mona, litheko tse phahameng tsa ts'ebeliso e mpe ea lithethefatsi kamora ho hlekefetsoa ha bana li ka hlalosoa karolo e 'ngoe ke khatello ea maikutlo ea ts'ebetso ea khatello ea kelello / corticolimbicAndersen le Teicher, 2008) jwaloka ha e sebelisoa ho lithethefatsi tsa tlhekefetso. Hypothesis ena e fana ka maikutlo a hore ho pepesetsoa khatello ea maikutlo ea bophelo ba bongoana ho etsa hore batho ba bang ba qhekellehe ho sebelisa lithethefatsi ba sa le banyenyane lilemong tse tharo tse latelang.

  1. Ts'ebeliso e mpe ea lithethefatsi e eketseha ka lebaka la "hypothalamic-pituitary-adrenal axis" e sebetsang haholoHyman et al., 2006).
  2. Ho pepesehela khatello ea kelello ho tsamaisana le linako tse tebileng tsa ho ba kotsing (Andersen le Teicher, 2008; Andersen le Teicher, 2004) e tla kenya letsoho tlokotsing ea tlhekefetso ea lithethefatsi. Matšoenyeho a bophelo ba bongoaneng a ka khetha hippocampus haholo le ho ntlafatsa karabelo maemong a amanang le lithethefatsi. Mathata a pele ho nako a ka eketsa ts'ebetso ea dopamine kahare ho bokaholimo ba letsoele, a etsa hore ho be le boemo ba mantlha ba anhedonia e etsang hore batho ba bang ba se ke ba batla lithethefatsi (Matthews le Robbins, 2003). Khatello ea bophelo hamorao e kanna ea khetha khetho ea "cortex ea pele"Leussis le Andersen, 2008), hape e eketsa tlokotsi ho mekhoa e amanang le lithethefatsi (Ernst et al., 2006; Brenhouse et al., 2008a).
  3. Libaka tsa likhoele tsa brain li hloka ho hola ho isa boholeng bo itseng bakeng sa phello ea ho pepeseha ha khatello ea maikutlo ho bonahala.

Ka bobeli, lits'ebetso tsena li eketsa tlokotsi ea ho sebelisa lithethefatsi le ho feto-fetoha le lilemo tsa ts'ebeliso ea pele pejana ho feta ka tloaelo ho bonoang ho batho ba sa sebelisoeng hampe. Re tla hlahloba bopaki bo tšehetsang liqeto tsena mme bo akaretsa lintlha tsena tse tharo.

1. Ponahalo ea mananeo a khatello ea maikutlo a rerection HPA

Ho pepesehela khatello ea maikutlo bongoaneng ho matlafatsa ts'ebetso ea karabelo ea khatello ea maikutlo, 'me ho fetole mekhatlo ea bona ea limolek'hule ho fetola kutloisiso ea bona le khethollo ea maikutlo (Caldji et al., 1998; Liu et al., 1997; Meaney le Szyf, 2005; Seckl, 1998; Weaver et al., 2004; Welberg le Seckl, 2001; E monyenyane, 2002). Liphetoho tsa limolek'hule tse bonts'itsoeng ho fihlela joale li kenyelletsa: (1) liphetoho tsa sebopeho sa moqomo oa GABA-benzodiazepine, tse hlahisang nts'etsopele ea methapo ea mali ea benzodiazepine le kamano e phahameng ea GABA-A receptors ho hippocampus, amygdala le locus coeruleus (Caldji et al., 2000a; Caldji et al., 2000b; Caldji et al., 1998; Hsu et al., 2003); (2) litheko tse phahameng tsa corticotropin e hlahisang li-hormone (CRH) mRNA maemong a amygdala le hypothalamus le ho fokotseha ha CRH mRNA ho hippocampus (Caldji et al., 1998; Liu et al., 1997); (3) e fokolitse ∝2 noradrenergic receptor density ho locus coeruleus (Caldji et al., 1998); le (4) phetoho ea epigenetic ka har'a methapo ea methapo ea DNA ea "hippocampal exon 17" glucocorticoid receptor (GR) papali ea papatso (Weaver et al., 2004; Weaver et al., 2006). Ka bokhutšoanyane, ka tsena, kapa liketsahalong tse ling tsa limolek'hule tse emetse ho sibolloa, mananeo a khatello ea maikutlo le maemo a kelello bokong hore a ba le maikutlo a ntlafatso a khatello, a sebelisanang le lintlha tse ling ho eketsa tšebeliso ea lithethefatsi le ho its'etleha.

Kamano lipakeng tsa khatello ea maikutlo le tšebeliso ea lithethefatsi

Khatello ea maikutlo e hlahisitsoe ho bapala karolo ea bohlokoa ho qaleng le ho boloka ts'ebeliso e mpe ea lithethefatsi 'me e fumanoe e le sesosa sa mantlha se lebisang ho oeleng hape ts'ebeliso ea lithethefatsi ho batho (Kreek le Koob, 1998). Litekong tse laoloang kelello khatello ea kelello e fumanoe e hohela litakatso tse matla tsa koae ho lithethefatsi (Sinha et al., 1999; Sinha et al., 2000). Boithuto bo fokolang bo ithutile litlamorao tsa tlhekefetso ea bongoana ho karabelo ea khatello ea maikutlo le taolo ea axis ea HPA. Banana (ba lilemo tsa 7-15 lilemo) ba nang le nalane ea CSA (n = 13) ba bonts'itse likhahla tse tlase le ovine CRH e hlohlelletsa maemo a ACTH a amanang le taolo (n = 13; (De Bellis et al., 1994a)). Maemo a cortisol a basal le plasma cortisol le maemo a susumetsang a ovine, leha ho le joalo, a ne a tšoana le ho bahlaseluoa ba CSA ho ba taolong. Liphetho tsena li ka bonts'a mofuta oa dysregulation ea HPA ka karabelo ea hypo-pituitary ho ovine CRH le karabelo e fetelletseng ea adrenal maemong a fokotsehileng a ACTH ho bana. Ka lehlakoreng le leng, Heim et al.,Heim et al., 2001) e tlaleha litlamorao tse fapaneng tsa dysregulatory tsa CSA ho batho ba baholos. Basali ba hlekefelitsoeng ntle le khatello e kholo ea khatello ea maikutlo ba bontšitse ho feta likarabo tse tloaelehileng tsa ACTH ho tsamaiso ea ovine ea CRA, athe basali ba neng ba hlekefetsa basali ba nang le khatello e kholo ea maikutlo le basali ba sithabetseng maikutlo ntle le tlhekefetso ea pele ba ne ba sentse likarabo tsa ACTH mabapi le taolo. Basali ba hlekefelitsoeng ntle le khatello e kholo ea khatello ea maikutlo ba bontšitse motheo oa tlase le ACTH e tsitsitseng mohopolo oa plasma cortisol. Ka mokhoa o ts'oanang, banna ba nang le nalane ea ho sithabela bongoaneng ba bontšitseng ho eketseha ha karabelo ea ACTH le cortisol ho dexamethasone / CRF. Karabelo e eketsehileng e ne e amahanngoa le ho teba, ho teba le ho qaleha ha tlhekefetso (Heim et al., 2008). Liphumano tsena li bonts'a hore maikutlo a ho ikamahanya le maemo a petohileng le maemo a arohaneng a adrenal cortex a etsahala ho batho ba hlekefelitsoeng ntle le khatello e kholo ea maikutlo kapa khatello ea khatello ea maikutlo.

Lithuto tsa mohlala oa liphoofolo li bontšitse hore khatello ea maikutlo e ama karabelo ho lithethefatsi tsa tlhekefetso ka mekhoa e mengata. Ho pepesehela maemo a sithabetsang khafetsa ho eketsa ho ikatisa hoa lithethefatsi tse lemalloang. Matšoenyeho a fapaneng a kenyeletsa khatello ea kelello e pheta-phetoang (Piazza et al., 1990), khatello ea maikutlo (Deroche et al., 1992a), khatello ea maikutlo sechabeng (Deroche et al., 1994), le khatello ea khaello ea lijo (Deroche et al., 1992a), e eketsa karabelo ea locomotor ho systemic amphetamine kapa morphine. Matšoenyeho a susumetsang a khatello ea maikutlo ho amphetamine le morphine a ipapisitse le axis e tsitsitseng ea HPA, mme ha e hlahe ho liphoofolo moo khatello ea khatello ea corticosterone e hatelletsoeng (Deroche et al., 1992a; Deroche et al., 1994; Marinelli et al., 1996). Ts'ebetso e pheta-phetoang ea corticosterone e le mong (ntle le ho pepesetsoa khatello ea maikutlo) e lekane ho ts'oara karabelo ea locomotor ho amphetamine, joalo ka khatello ea bokhachane e bileng teng ka lebaka la thibelo ea bo-mme nakong ea beke ea ho qetela ea boimana (Deroche et al., 1992b). Glucocorticoids ka boeona e na le litlamorao tse tobileng ho batho ba bang le ho tiisa thepa mehlolong ea liphoofolo, joalo ka bopaki ba nts'etsopele ea taolo ea corticosterone e kenang kahare, e etsahalang maemong a plasma corticosterone ha a bapisoa le a hlohlellelitsoeng ke khatello ea maikutlo (Piazza et al., 1993). Leha ho le joalo, ho na le liphapang tse kholo tsa batho ka bomong tsa ho ikamahanya le boits'oaro ba corticosterone (Piazza et al., 1993).

Mohlomong, ntho ea bohlokoahali ke hore ho pepesetsoa lintho tse fapaneng tse fapaneng tse fumanoeng ho thusa ho khutlisa ho batla ha heroine ho sa feleng.Shaham le al., 2000; Shaham le Stewart, 1995), cocaine (Ahmed le Koob, 1997; Erb et al., 1996), joala (Le et al., 2000; Le et al., 1998), le nicotine (Buczek et al., 1999). Lithutong tse ling khatello ea maikutlo e bile le phello e matla le ho feta ea ho khutlisetsa bohloko ho feta ho pepesehela sethethefatsi (Shaham le al., 1996; Shaham le Stewart, 1996). Khatello ea kelello e khutlisetsa likhetho tsa sebaka seo se kileng sa hlakisoa ke lithethefatsi (Wang et al., 2000). Metyrapone (e thibelang secretion ea corticosterone e hatelloang ke khatello ea maikutlo empa e sa fetole maemo a basort corticosterone) e hlahisa khatello e tlisoang ke khatello ea boits'oaro ba koae, ntle le ho tsitlallela pherekano e mpe ea boits'oaro ba motor kapa boits'oaro bo tsamaisang lijo (Deroche et al., 1994).

Qetellong, lithuto tsa pele li bonts'itse hore khatello ea maikutlo ke ntlha e hlahelletseng ho qaliso, phepelo le ho khutlisetsoa hoa tšebeliso ea lithethefatsi (Deroche et al., 1992a; Erb et al., 2001; Goeders, 1997; Kabbaj et al., 2001; Piazza et al., 1990; Shaham le al., 2000; Shalev et al., 2002; Shalev et al., 2001; Stewart, 2000). Likarabo tsa khatello ea maikutlo tse ntlafalitsoeng kapa tse mpe ka lebaka la tlhekefetso ea bana, bonyane ka karolo e itseng, li ka qobella tlokotsi e eketsehang ea baphonyohi ba tlhekefetso bokhobeng ba lithethefatsi (McEwen, 2000a; Rodriguez de Fonseca le Navarro, 1998; Sinha, 2001; Stewart et al., 1997; Triffleman et al., 1995).

2. Ho pepesehela khatello ea maikutlo ho tsamaisana le linako tse tebileng tsa tlokotsi tse tla kenya letsoho tlokotsing ea tlhekefetso ea lithethefatsi

Nako ea thohako le eona e ka bapala karolo e nyelisitsoeng ts'ebeliso e mpe ea ts'ebeliso ea lithethefatsi. Lisebelisoa tsa neurotransmitter tsa motho ka mong kapa libaka tsa boko li hlaseleha habonolo ke litšusumetso tsa kantle nakong ea lifensetere tse ikhethang tse tsejoang ka linako tse tebileng. Linako tse hlakileng li amahanngoa le liketsahalo tsa kholo ea neurogeneis, phapang, le pholoho (Andersen, 2003; Bottjer le Arnold, 1997; Harper et al., 2004; Heim le Nemeroff, 2001; Koehl et al., 2002; Nowakowski le Hayes, 1999; Sanchez et al., 2001). Leha lits'ebetso tse hlalosang nako e mahlonoko li sa tsejoe, mekhoa e hlakileng ea phetoho e kenyelletsa, empa ha e felle feela, phetoho ea methapo ea ho lokisa boko, polelo e fetotsoeng ea lintlha tsa neurotrophic, le nts'etsopele ea methapo ea methapo. Liphetoho ho efe kapa efe ea lintlha tsena ka nako e thata li hlahisa phello e sa feleng sebopeho le tšebetsong (Adler et al., 2006; Andersen, 2003). Joalokaha ho hlahlojoa ka tlase, khatello ea pele ea bophelo e ama lits'ebetso tse ngata tse bopehileng bokong.

Ho eketseha ha khatello ea maikutlo ho fetola tsoelo-pele ea boko

Liphetoho tsa axis ea HPA li eketsa khatello ea khatello ea maikutlo (tenet #1), empa liphetoho tsena li na le litlamorao tse ikhethang ntlafatsong ea kelello. Litlamorao tse matla le tse kholo tsa CRH (Brunson et al., 2001) le lihormone tsa khatello ea maikutlo, sebetsa ka konsarete le li-neuromodulators tsa monoamine le li-amino acid tse thabisang (McEwen, 2000b), ho fetola mekhoa ea mantlha ea neural. Tsamaiso ea li-glucocorticoids nakong ea bophelo ba pele ho liphoofolo tsa laboratori li fokotsa boima ba boko le ka botlalo dikahare tsa DNA (Ardeleanu le Strerescu, 1978), e hatella kamora ho hlaha ha lisele tsa granule ho "cerebellum" le "meno" a morao-raoBohn, 1980), e kena-kenana le karohano ea lisele tsa glial (Lauder, 1983), le ho fokotsa palo ea methapo ea methapo (dendritic spine) libakeng tse fapaneng tsa boko (Schapiro, 1971). Mosebetsi oa morao-rao o bontša ka ho hlaka hore ho pepesetsoa lipontšo tsa limolek'hule tse susumetsang khatello ea maikutlo ho ama myelination (Leussis le Andersen, 2008; Meyer, 1983; Tsuneishi et al., 1991), neuronal arborization (McEwen, 2000b), neurogeneis (Gould le Tanapat, 1999; Mirescu le Gould, 2006), le synaptogeneis (Andersen le Teicher, 2004; Garcia, 2002).

Litlamorao tsa khatello ea kelello bokong, leha ho le joalo, ha li hohle. Likarolo tse ikhethang tsa boko li fapana ka kutloisiso ea bona ea maikutlo le lits'usumetso tse tlisoang ke khatello ea maikutlo. Ho ts'oaroa ke letsoalo ho ka susumetsoa ke liphatsa tsa lefutso (Caspi et al., 2002; Caspi et al., 2003; Koenen et al., 2005), bong (Barna et al., 2003; De Bellis le Keshavan, 2003; Teicher et al., 2004), nakoAndersen, 2003; Andersen et al., 2008; Leussis le Andersen, 2008; Perlman et al., 2007), letsoalo la li-receptor tsa glucocorticoid (Benesova le Pavlik, 1985; Haynes et al., 2001; McEwen et al., 1992; Pryce, 2007), le boholo ba li-neuron tsa lehae ho lokolla CRH ho arabela khatello ea maikutlo (Chen le al., 2004). Thutong ena, re shebisisa hore na nako ea ho pepesoa ha khatello ea maikutlo e ka tsamaisa polelo ea tšebeliso e mpe ea lithethefatsi joang ka liphetoho tsa boko ba tikoloho. Libaka tsa brain tse hlahang li bontša ho ba kotsing ea morphometric litlamorao tsa khatello ea maikutlo kapa tlhekefetso ea bongoana ho kenyelletsa Corpus callosum, hippocampus, cerebellum le neocortex (Andersen et al., 2008). Ho qala, re tla tšohla phello e liehang ea khatello ea bophelo ba pele ho hippocampus, e hlahang lipakeng tsa bocha le ho ba motho e moholo.Andersen le Teicher, 2004). Liphetoho ho li-nucleus accumbens le preortalal cortex le tsona li tla tšohloa.

Mathata a pele a ama nts'etsopele ea hippocampus

Lipatlisiso tse kopaneng tsa kliniki le tsa preclinical li fana ka maikutlo a hore ho pepesetsoa khatello ea maikutlo nakong ea bophelo ba bongoana ho hlahisa litholoana tse liehang ho nts'etsopele ea hippocampal. Liphetoho tsa molumo oa hippocampal li bonahala li le teng nakong ea kholo. Lithuto tsa tleliniki tse hlahlobang moroko oa mafu a hippocampal ho baphonyohi ba tlhekefetso ea bana ba hlokometse tahlehelo e kholo ea bolengAndersen et al., 2008; Bremner et al., 1997; Mokhanni et al., 2000; Stein, 1997; Vermetten et al., 2006; Vythilingam et al., 2002). Ho fapana le hoo, liphuputso tse entsoeng ho bana ba hlekefelitsoeng ba nang le PTSD li ile tsa sitoa ho fumana bopaki ba tahlehelo ea molumo oa hippocampal (Carrion et al., 2001; De Bellis et al., 1999b; De Bellis et al., 2002), hape, ho tlalehiloe keketseho e kholo ea bonyata ba litaba tse tšoeu ((Tupler le De Bellis, 2006). Kahoo, litlamorao tsa tlhekefetso ea bongoana li amahanngoa le tahlehelo ea molumo oa hippocampal ho motho e moholo, empa eseng nakong ea bongoana kapa bohlankana ba pele (Andersen et al., 2008; Teicher et al., 2003). Re sa tsoa fumana phokotso ho bophahamo ba lefatše hippocampal bate e latelang CSA mohlaleng oa batho ba baholo ba bangata haholo haeba tlhekefetso e etsahetse lipakeng tsa lilemo tsa 3-5 le pakeng tsa 11-13 ea lilemo liAndersen et al., 2008). Linako tsena li tsamaellana le likarolo tse ngata tsa tlhahiso ea batho e ngata haholo (Gogtay et al., 2006). Ho shebella esale pele ho bonahala ho kopanya liphetho tsena tse neng li bonahala li sa lumellane lipakeng tsa lithuto tse hlahlobang bana kapa batho ba baholo. Khatello ea pele ea nako ea ho itšehla thajana e thibela phepelo e tloaelehileng ea peripubertal ea li-synapses ho CA1 le CA3 sebakeng sa hippocampus ea likhoto; leha ho le joalo, khatello ea maikutlo ea pele ha e thibele ho mela, e isang khaellong ea bofokoli bo sa feleng ba bongoana / ho ba motho e moholo lilemong (matsatsi a 60 a lilemo ho rat)Andersen le Teicher, 2004). Kahoo, ho ka etsahala hore ho pepesehela khatello ea maikutlo ea pele ho fetola khatello ea kholo ea kholo ea hippocampal, ka phello e mpe ea khatello ea maikutlo e bonahala nakong ea phetoho ea ho tloha bohlankaneng ho ea ho motho e moholo.

Karolo ea hippocampus ke ho fana ka tlhahisoleseling ea boitsebiso bo tsoang selomong sa pele ho boemo ba li-nucleus accumbens (Mohau et al., 2007), ka hona e kenella lits'ebetsong tsa tlhokomeliso ea lithethefatsi. Ho lahleheloa ke letsoalo la hippocampal synaptic, kapa bokhutšoanyane ba lintho tse bokhutšoaane, tse hlahang likhatellong tsa pejana li pepesa batho ka bomong ha ba feta lilemong tsa bocha li ka kena-kenana le kapa tsa fetola tšebetso ena ea liphatsa tsa lefutso. Hajoale, ha ho tsejoe letho ka litlamorao tsa liphetoho tse tlisoang ke khatello ea maikutlo nakong e tlang mabapi le ho ba tlokotsing ea tlhekefetso ea lithethefatsi. Leha ho le joalo, liso tsa lethoto la lethoping la "hemopampamine" bekeng ea pele ea bophelo literekeng li eketsa palo le boits'oaro ba tšebeliso ea lithethefatsi, empa eseng sebaka sa khefutso lenaneong le tsoelang pele la boitaolo ba methamphetamine (Brady et al., 2008). Lintlha tsena li tsamaisana le ho kenella ha lipontso tsa cortical ka har'a li-bokello, 'me li ka fa mocha ea pepesitsoeng khatello ea ts'ebeliso e mpe ea lithethefatsi a sa le monyane ho feta lithaka tsa hae. Tlhaloso e 'ngoe e ka ba hore liphetoho tse susumetsoang ke khatello ea maikutlo ea hippocampal li fokotsa taolo e mpe ea maikutlo a HPA axis (tenet #1; Goursaud et al., 2006). Liphumano tsa ho ba kotsing ea ho sebelisa lithethefatsi ka mor'a ho fetoloa ha hippocampal lithutong tsa preclinical li lumellana le liphetho tsa kliniki tse boletsoeng ka holimo.

Mananeo a nts'etsopele a khatello ea maikutlo a nts'etsopele ea sheramines dopamine system bakeng sa moputso o fokolisitsoeng le anhedonia e phahameng

Ho thehiloe hantle hore ho pepesehela khatello ea bophelo ba bongoaneng ho eketsa maikutlo a dysphoria, anhedonia, le matšoenyeho (Ruedi-Bettschen et al., 2006). Tlhahlobo e hlakileng, e phethahetseng e hlahisitsoeng ke Matthews le Robbins ho 2003 (Matthews le Robbins, 2003) e fana ka maikutlo a hore khatello ea pele ea bophelo e nyenyefatsa ts'ebetso ea moputso. Ho arohana ho atamelaneng ha bo-mme ho amana le ho fokotsa ho fokotseha ha likarabo tsa boits'oaro ho takatso ea takatso ea lijo mohopolong oa batho ba baholo ha o bapisoa le taolo e sebetsanoang (Matthews le al., 1996). Joalokaha ho hlokometsoe lits'ebetsong tse fapaneng tsa liteko, ho kenyelletsa boits'ebetso, ho itlhasimolla ha batho le ho khetha lintho tse ikhethileng, tlhaiso-leseling e fana ka maikutlo a hore mohopolo o susumetsang o tsosa likarabo tse matla litekatsong tse arohaneng (Matthews le Robbins, 2003). Mohlala, likhoto li ikhethile li bonts'a litla-morao tse ntle le tse mpe tse mpe ka ho ikatisa joalo ka tharollo ea bapisi, ho fana ka maikutlo a fokotsehile a ts'ebetso ea meputso khothatsong ena ea tlhaho (Matthews le Robbins, 2003). Ts'ebeliso ea lithethefatsi e thusa ho hlola maikutlo ana a anhedonia, mme ho latela hore taba e hatelletsoeng e tla ba le hloko haholoanyane litlamorao tsa lithethefatsi leka ho etsa hore boemo bona ba basal bo fetohe.

Ho pepeseha ha khatello ea maikutlo ho sebetsa, ka ho fetola ts'ebetso ea dopamine (DA) kahare ho li-bokellase tsa nucleus. Ho ipapisitse le liphetho tsa batho ba baholo tsa ho nyahama ha bo-mme, bopaki ba boits'oaro, joalo ka keketseho ea ts'ebetso ea popomotor ho arabela bocha.Brake et al., 2004), ho koae ka koae (Brake et al., 2004), le ho hatella khatello ea maikutlo ho ts'ehetsa maikutlo a hore ho nyaroha ha 'm'ae ho matlafatsa kutloisiso ea motheo ea DA ka har'a li-nucleus accumbens. Re fumane hore ho nyahlatsoa ha bo-'m'e nakong ea bokhachane ho eketse litaba tsa DA le ho fokotsa tlhahiso ea serotonin (tekanyetso ea 5-HT / 5-HIAA) ka har'a li-nucleus accumbens le amygdala nakong ea ho ba motho e moholo.Andersen et al., 1999). Tekanyo e tobileng e bonts'a hore batho ba ikhethileng ba le maemong a phahameng a DA sebakeng sena ho arabela cocaine (Kosten et al., 2003), phello e ka ananeloang ke maemo a tlase a morekisi oa DA (Brake et al., 2004; Meaney et al., 2002). Litlamorao tsa khatello ea maikutlo ho li-bokellus tsa nucleus, ha li felle feela liketsahalong tsa bophelo ba pele. Hall et al (Hall et al., 1998) e fumane hore khatello ea kamora ho khoesa kamore ea ho emisa ho ba boinotšing e hlahisitse ho fokotseha ho sa feleng ha maemo a 5-HIAA le keketseho ea maemo a DA le ho eketsoa ha tokollo ea DA e susumetsang e nyarosang ea li-nucleus accumbens. Ka hona, khatello ea maikutlo e sa feleng e ka eketsa monyetla oa ts'ebeliso e mpe ea lithethefatsi ka ho fetola nts'etsopele ea tsamaiso ea mesolimbic DA, empa litlamorao tsa khatello ea maikutlo li ka hlaha lilemong life kapa life.

Mokhoa o mong oo ho ka etsahalang hore ebe ona, keketseho e tsitsitseng ea li-alebens DA o hlahisa maikutlo a dysphoria mme anhedonia ke ka ts'ebetso ea eona ho ts'ebetso ea transcriptal factor factor, CREB (Nestler le Carlezon, 2006). Haholoholo, leha ho le joalo, maemo a CREB a eketsehileng a ne a sa bonoe liphoofolong tse arohaneng tsa bo-mme (Lippmann et al., 2007) hape o fana ka maikutlo a hore anhedonia e ka tsamaisoa ke mochine o mong kapa ea fetoha sebakeng se seng bokong. Litlamorao tsa Corticosterone le / kapa CRH tsamaisong ea mesolimbic DA li ka feto-fetola molumo o susumetsang khatello ea maikutlo mabapi le litekanyetso tsa boitšoaro ho lithethefatsi tsa tlhekefetso (Barrot et al., 1999; Deroche et al., 1995; Koob, 1999; 2000; Marinelli le Piazza, 2002; Piazza et al., 1996; Rouge-Pont et al., 1998; Boithati, 1998). Ho imeloa kelellong ho sa foleng ho hlahisa liphetoho tsa methapo ea kutlo ka har'a li-nucleus accumbens - ventral tegmental sebakeng se ts'oanang le litlamorao tsa ho pepeseha ha lithethefatsi (Fitzgerald et al., 1996; Ortiz et al., 1996).

Ho pepesetsoa tlhekefetso ea bongoana ho ka eketsa kotsi ea tlhekefetso ea lithethefatsi ka ho ama tsamaiso ea DA le kutloisiso ea maikutlo ho tse matlafatsang. Tlhekefetso ea bongoaneng e amahanngoa le maemo a eketsehang a pherekano ea DA kapa Homovanillic acid (De Bellis et al., 1999a; De Bellis et al., 1994b), le litekanyetso tsa plasma tse theotsoeng tsa dopamine beta-hydroxylase (Galvin et al., 1995) enzyme e ikarabellang bakeng sa ho fetola DA hore e be norepinephrine.

Matšoenyeho a bongoaneng a ama cortex ea pele

Ho fapana le litla-morao tse liehisitsoeng tsa khatello ea maikutlo ho hippocampal morphometry, khatello ea maikutlo e fana ka litlamorao tse kholo ho cortex ea pele nakong ea bohlankana (Andersen et al., 2008; Hall, 1998; Leussis le Andersen, 2008). Ho feta moo, litla-morao tsena lia bonahala ntle le tšenyo ea nako joalo ka ha ho bonoa bakeng sa hippocampus (Andersen le Teicher, 2004). Nts'etsopele e tsoetseng pele ea cortex ea pele (Crews et al., 2007; Spear, 2000) e ka etsa hore e angoe habonolo ke litlamorao tsa khatello ea maikutlo nakong ea bohlankana. Ntle le moo, li-receptor tse phahameng tsa glucocorticoid li hlahisoa ka cortex nakong ena, e ka eketsang litlamorao tsa khatello ea maikutlo (Pryce, 2007). Ho pepesetsoa khatello ea maikutlo nakong ea bohlankana, ho kenyeletsoa CSA lithutong tsa bongaka (Andersen et al., 2008) kapa ho ikarola sechabeng lithutong tsa pele (Hall, 1998; Leussis le Andersen, 2008), e amahanngoa le ho fokotseha hoa lintho tsa bohlooho tsa pelepele le letsoele la synaptic, ho sa fetoloeng liphetoho lipolotiking tse ling tsa boko. Ho ipapisitsoe le lithuto tsa pharmacological, tahlehelo ena ea "synaptic" e bonts'a keketseho e bakoang ke khatello ea maikutlo mesebetsing ea glutamatergic (Leussis et al., 2008). Ts'ebetso e ntlafalitsoeng ea glutamatergic ka pele ho cortex e lumellana le likarolo tse eketsehileng tsa maemo a lithethefatsi tsa tlhekefetso (bona tenet #3).

Ka sebele, liphuputso tse ileng tsa hlahloba kamano pakeng tsa khatello ea bongoana le tšebeliso e mpe ea lithethefatsi li bontša ho ba kotsing e eketsehileng. Litlaelese tsa Ibotenic tsa "cortex" ea mori o tlang pele ho likhoto, tse hlahisang ho bolokoa ha li-accumbens, li felletse ka karabelo e kholo ea boitšoaro ho imeloa kelellong le ho eketsa khatello ea maikutlo e tlisoang ke dopamine ho li-drabens (Brake et al., 2000). Ho itšunya-tšunye ho ile ha holisoa, empa eseng likhoto tsa bo-'m'ae tse hlokahalitsoeng, tse bonts'itseng maikutlo a sebaka sa 1.5 mg / kg amphetamine (Weiss et al., 2001). Tabeng ena, lithethefatsi tse hlahisang bokhoba ba takatso ea lithethefatsi tse amanang le cue tse phahameng (ke hore, heroin le Crack (Franken et al., 2003)) a kanna a angoa ke ho ameha ke khatello ea maikutlo kamora nako. Joalokaha ho buisanoe ka tenet #3, cortex ea pele e kenyelletsa polelo ea boits'oaro ea ho batla lithethefatsi hang ha ho thehoa mokhatlo oa lithethefatsi.

3. Boemo bo itseng ba ho feto-fetoha ha maikutlo a bokong bo hloka ho hlaha bakeng sa litlamorao tsa ho pepeseha ha khatello ea kelello ho bonahala

Nako ea bocha e bontša monyetla oa ho lemalla lithethefatsi, le ha ho e-na le phapang e kholo lilemong tsa ho qala kahare ho sehlopha ka seng sa lithethefatsi (bona Setšoantšo sa 2). Joalo Setšoantšo sa 2 e bonts'a, ts'ebeliso ea lithethefatsi ha e qalisoe ho 50% ea sechaba ho fihlela lilemong tsa bocha (tenet #3). Sena se bonahala e le 'nete ho lihlopha tsohle tsa lithethefatsi. Lipalopalo li bonts'a hore ho qaleha ha ts'ebeliso ea lithethefatsi haholo ho eketsa kotsi ea ho ts'oaroa le ts'ebeliso ea bokhoba ba bophelo bohle (Hill et al., 2000; SAMHSA, 1999). Mohlala, kotsi e eketsehileng ea botaoa ba joala e eketsa 40% bakeng sa ba qalang ho nwa pele ho lilemo tsa 15 (SAMHSA, 1999). Ka mokhoa o ts'oanang, kotsi e lekanang ea ts'ebeliso ea koae ka mor'a ho pepesetsoa pepeneneng e na le menyetla e mene haeba ts'ebeliso e qalile pele ho lilemo tsa 12, 'me e fokotseha haholo ka selemo se seng le se seng sa ho khaotsa ho tsuba (O'Brien le Anthony, 2005). Ho beha kotsing ea ho tsuba matekoane le koae le ho tsuba hape hoa eketseha haeba ho hlahella nakong ea bocha.Waylen le Wolke, 2004; Westermeyer, 1999). Mona, re phahamisa khopolo-taba ea hore ho pepesetsoa khatello ea maikutlo nakong ea ts'ebetso e tebileng (tenet #2) e boetse e na le liphetho ka ho hlahisa phetoho ea letsohong la ho qala ts'ebetso ea liteko tsa lithethefatsi.

Setšoantšo sa 2

Nako ea ts'ebeliso ea pele ea mefuta e fapa-fapaneng ea lintho tse ke keng tsa qojoa. Lintlha li reriloe e le liperesente tse eketsehang tsa basebelisi ba felletseng ba mofuta o itseng oa ntho e senyehang ka lilemo tsa ts'ebeliso ea pele. Lintlha li ile tsa bokelloa ke Phuputso ea Naha ea Ts'ebeliso ea Lithethefatsi le Bophelo, 2002 ...

Tenet #3 e fana ka maikutlo a hore litlamorao tsa khatello ea mantlha mabapi le ts'oaetso ea ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea ts'ebeliso ea lintho habonolo li lula li le lerootho ho fihlela lilemong tsa bocha, joalo ka ha hypothesised bakeng sa schizophrenia (Weinberger, 1987), ho tepella maikutlo (Andersen le Teicher, 2008; Teicher et al ka khatiso), le ho pepesetsoa lithethefatsi kapele (Andersen, 2005). Liketsahalo tsa bophelo ba pejana li fana ka mohlala oa nts'etsopele o ntseng o tsoela pele ho fihlela bocheng le ho ba motho e monyane lilemong. Litlamorao tse ling tsa khatello ea maikutlo li bonahala habonolo haufinyane, ho kenyelletsa le liphetoho tse etsahalang hape (Leussis le Andersen, 2008; Radley et al., 2005). Tse ling, joalo ka ho kenella ka har'a letsoalo la hippocampal synaptic, li ka hlaha hamorao bophelong.Andersen et al., 1999; Andersen le Teicher, 2004). Re etsa tlhahiso ea hore liphetoho tsa maturational ho cortex ea pele, e bapala karolo ea bohlokoa ho batleng lithethefatsi le ho khutla, e ka ba senotlolo sa ho utloisisa ho qala ha bohlankana ho tlhekefetso ea lithethefatsi.

Ts'ebetso ea ts'ebeliso ea lithethefatsi e kenyelletsa karolo e matla, e susumetsang e ntlafalitsoeng hape ke mekhoa e amanang le ho ts'oara lithethefatsi mme e nkuoa e le eona ntho ea bohlokoa ea ho khutla hape (Kalivas le al., 2005; Volkow, 2005; Robinson le Berridge, 1993; Vezina le Stewart, 1984)). Boitsebiso bo tsoang lithutong tsa menahano ea batho bo bonts'a hore litloaelo tse amanang le ts'ebeliso ea lithethefatsi le litakatso (ke hore, tikoloho ea tikoloho, paraphenalia) ho batho ba kenya ts'ebetso ea lipotoloho tse ka pele mokotleng o ka pele o kenyelletsoeng ts'ebetsong ea moputso (Goldstein le Volkow, 2002; Grant et al., 1996; Maas et al., 1998; Tzschentke, 2000). Tlhahisoleseling ena e sebelisetsoa ho hakanya boleng ba tšusumetso ea litefiso tse ipapisitseng le moputso o ka bang teng (Elliott et al., 2003; London et al., 2000) hape e hlahisa mohopolo o khothalletsoang (takatso ea lithethefatsi) (Childress et al., 1999). Nakong ea maemo a seng tlatsetso, ts'ebetso ea GABA e ntlafatsa maemo a boitšoaro ka ho lumella mehloli e mengata ea tlhahisoleseling ho fetola tlhahiso ea glutamate (Li-Seamans le Yang, 2004). Leha ho le joalo, tlasa maemo a khothalletsang bokhoba le ho oela hape, li-receptors tsa D1 li hlalosoa ka mokhoa o ikhethileng ho li-neuron tse mpe tse projeke ho li-accumbens. Ka lebaka leo, keketseho e khahlehang ea copamine ea ts'ebetso ea dopamine e na le monyetla oa ho hlohlelletsa tsela ena le ho ntlafatsa boits'oaro ba lithethefatsi ka litšenyehelo tsa boits'oaro bo bong (ke hore, boitšoaro bo fokotsehileng; Setšoantšo sa 1; (Kalivas le al., 2005)).

Ho fetoha ha kelello ea bongoana ho amana le ho ba kotsing ea ho etsa lintho tse amanang le lithethefatsi

Patlisiso ea EpidemiologicalSetšoantšo sa 2) e bonts'a hore bokhoba bo bongata ha bo hlahe ho fihlela lilemong tsa bocha. Phetoho ea "cortex" ea mantlha le khokahano ea eona libakeng tse ling e kanna ea ba taba ea bohlokoa nakong ea ts'ebetso ena (Ernst et al., 2006). Phapang e ntlafalitsoeng ea ts'ebetso ea moputso e bonoe lithutong tsa BOLD fMRI ho bana. Karabelo e ka pele ea bokhoni ba ho amohela moputso e ea nyonyeha le ho feta ha e bapisoa le batho ba baholo (Durston, 2003). Ka lehlakoreng le leng, bana ba bonts'a ts'ebetso e kholo ho li-accumbens (Ernst et al., 2005). Ho feto-fetoha ha maemo ho lebisa tloahelong e fokolang ea mosebetsiRubia et al., 2000), eo mohlomong e bonts'ang khokahano ea likhokahano tsa synaptic.

Ho aha ka mosebetsi oa Kalivas et al, Brenhouse le basebetsi 'moho le Brenhouse, 2008 #7113} haufinyane o bonts'itse hore li-receptor tsa D1 dopamine ho li-fiber tse kenang ho tloha cortex ea pele ho isa ho li-bokellase tsa nucleus hangata li hlahisoa ka nako ea bohlankana, empa li-receptors tsa D1 sebakeng sena. 'me e fumanehang litselaneng tsena li tlaase ho liphoofolo tse monyane le tse tsofetseng. Pono ena e lumellana le lithuto tsa pele ho lithupelo tse buileng ka hore litlatsetso li fokolitse litlamorao libakeng tsa bokong bo amanang le liketso tse tlisoang pele ho nako ea bocha (Andersen et al., 2001; Leslie et al., 2004). Ho eketsa li-receptor tsa D1 sebakeng sa pele sa cortex ho matlafatsa kutloisiso ho tikoloho / likokoana-hloko tse amanang le cocaine lilemong tsa bocha, tse hlokang litekanyetso tse tlase tsa cocaine ho feta liphoofolo tse nyane kapa tse tsofetseng ho etsa liphetho tsa bohlokoa sebakeng (Badanic et al., 2006; Brenhouse et al., 2008a). Ha e se e thehiloe, mekhatlo ena ea bacha ea lithethefatsi e hanang ho felisoa ho feta mekhatlo ea batho ba baholo (Brenhouse le Andersen, 2008b). Ka kakaretso, tenet #3 e fana ka maikutlo a hore boits'oaro bo joalo ba bokhoba bo tla ka nako ea bocha ho batho ba imetsoeng le ba seng khatello ea maikutlo hobane karolo e 'ngoe ea eona e le matla.

Eya ho:

Nahanisisa

Ho pepeseha litsietsing tsa pele ho tla fetolela ho batla lithethefatsi ho isa lilemong tsa pejana ka fensetereng ena, empa hore na liphetoho tsena li ka lebaka la liphetoho mokhoeng oa hippocampus (khatello ea maikutlo ea pele), dopamine e phahameng ho li-accumbens (khatello ea maikutlo ea pele), kapa liphetoho tse feto-fetohang preortalal cortex (khatello ea bohlankana) e ntse e lokela ho tsejoa. Moetso o khothalletsoang oa tšebeliso ea lithethefatsi ntle le mariki o bontšoa ho Setšoantšo sa 1. Ka bobeli, lintlha tse hlahlojoang thutong ena li fana ka maikutlo a hore mokhoa oa moputso o ntlafalitsoe. Mokokotlo oa HPA o sa sebetseng o ka etsa hore motho a sebelise ts'ebeliso e matla, athe anhedonia e eketsa ts'ebetso ea kotsi ea ts'ebeliso le ts'ebeliso. Mariki a tloaelehileng a fokotsang ts'ebeliso ea lithethefatsi, a fumanoang hippocampus le cortex ea pele, ha a sebetse 'me a ka tsamaisa ts'ebetso ea ts'ebeliso ea lithethefatsi ho feta kamoo ho neng ho lebelletsoe. Tlhahlobo ena e fana ka bopaki ba hore ho pepesehela liketsahalong tse mahlonoko nakong ea ntlafatso ho etsa hore motho a se ke a sebelisa lithethefatsi hampe pejana ho batho ba sa hlekefetsoang. Ho utloisisa karolo eo nts'etsopele e e phethang ho bonts'a mabaka ana a kotsi hangata ho hlokomolohuoa, empa ho hloka tlhokomelo e eketsehileng ho utloisisa ka botlalo phello ea khatello ea bophelo ba pele (CSA, karohano ea bo-mme) ho tlhekefetso ea lithethefatsi. Ehlile litla-morao tsa mathata a pele li ka lieha ho hlahisoa, empa li bonahala ka tšohanyetso nakong ea bohlankana. Ho lieha hona ha qalong ho ka fana ka mohopolo o seng kotsi oa polokeho ea hore litsietsi tsa pele ha lia ka tsa lematsa motho ka nako e telele. Leha ho le joalo, ho lieha hona ho ka fana ka monyetla oa monyetla oa hore mekhoa ea ho kenella pele e ka thibela tšusumetso ea litsietsi tsa nts'etsopele.

Eya ho:

Liteboho

E tšehelitsoe, ka karolo e itseng, ka likhau tse tsoang NarsAD (2001, 2002, 2005), NIDA RO1DA-016934, RO1DA-017846), NIMH (RO1MH-66222) le li-Simches le Rosenberg Malapa. MHT e ne e le mohlahlobisisi oa John W. Alden Trust.

Eya ho:

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

Eya ho:

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