Ọgwụ Ọjọọ Dị Ka Ihe Nlereanya nke Neuroplasticity (2007)

1. ¹Ngalaba nke Neurosciences, Mahadum Medical South Carolina, Charleston, SC, USA
2. ²Ngalaba Ọrịa Isi, Philadelphia VA Medical Center, Mahadum Pennsylvania, Philadelphia, PA, USA

Mmekọrịta: Dr P Kalivas, Ngalaba nke Neurosciences, Mahadum Medical South Carolina, 173 Ashley Ave, BSB 410, Charleston, SC 29425, USA. Tel: + 1 843 792 4400; Fax: + 1 843 792 4423; E-mail: [email protected]

nkịtị

MGBE Ọ BỤ Ọ BỤ Ọ BỤ Ọ BỤ Ọ BỤ Ọ BỤ Ọ BỤ ỊDỤTA

Maka nyochaa a, a ga-ejikwa arụ ọrụ rụọ ọrụ abụọ: ụzọ nke mbụ, mgbanwe na-adịghị agbanwe agbanwe nke ọrụ ntanetị nke na-aga n'ihu ruo ọtụtụ izu nke abstinence ọgwụ, na nke abụọ, mgbanwe siri ike na-agbanwe site na izu iji bụrụ mgbanwe na-adịgide adịgide. Mkpụrụ obi na-agbanwe agbanwe na-adabere na mgbanwe ndị dị mkpa bụ ndị na-eme ka ha nwee ike ịmepụta àgwà ọhụrụ, ebe ọ bụ na nzụlite anụ ọkụkọ kwekọrọ n'ozizi anụ ahụ nke a napụtara iji duzie mmebi nke omume mmụta. Maka ọgwụ riri ahụ, a na-akọwakarị akụkụ ndị a dịka ịmalite ịrịa ahụ (ntụgharị, ịmụta ịghọ onye ahụ riri ahụ), na ebe obibi dị jụụ na-enwe ike ịlọghachite mgbe ị kwụsịrị ịṅụ ọgwụ ọjọọ. A na-enweta mmepe nke riri ahụ site na iji ọgwụ ọjọọ eme ihe ugboro ugboro, na-agụnye ọtụtụ mgbanwe dị mkpirikpi nke ụbụrụ na ụbụrụ na-adabere n'ụzọ dị ukwuu na nkà mmụta ọgwụ ndị dị ndụ nke ọgwụ ahụ n'onwe ya (Nestler, 2005). Na Nyocha 1a, a na-ezo aka na oge a dị ka ihe gbasara ọha. A na-arụ ọrụ nke abụọ site na mkparị ọjọọ na-adabere na mgbanwe dị na synaptic physiology nke ụbụrụ ụbụrụ na-achịkwa ụbụrụ na mmetụta uche na-azaghachi ihe dị mkpa gburugburu ebe obibi. E gosipụtara nke a na Nyocha 1a dị ka ụzọ abụọ nke nlọghachi. Akụkụ mbụ nke nlọghachị a kọwara dị ka nlọghachị azụmagha, nke abụọ dị ka nlọghachị ike. Nghaghachi azụ a na-achịkwa na-ezo aka n'usoro mkpebi ikpe dị nkenke nke onye ahụ maara ahụ ji kpebie ịghaghachi azụ. Dịka ọmụmaatụ, onye ahụ nwere ike ime nhọrọ n'etiti inyere nwa ha aka na ụlọ akwụkwọ ma ọ bụ ịṅụ otu iko mmanya. Na nke a, onye ahụ na-eri ahụ na-emekarị nhọrọ dị mma nke obodo. Na nlọghachi ahụ ike, onye ahụ riri ahụ adịghị eme nhọrọ dị mma. Dịka ọmụmaatụ, ọ bụ ezie na inyere ụmụ ha aka ịrụ ọrụ ụlọ nwere ike ịbụ ihe gbasara ihe mgbaru ọsọ maka mgbede, ikpughe ihe dị iche iche gburugburu ebe obibi ma ọ bụ nrụgide nke onye ahụ jikọtara ya na iji ọgwụ ọjọọ eme ihe na-eme ka ịchọọ ọgwụ, ma ọ dịghị eme mkpebi ọ bụla, onye ahụ nlọghachite na-akpaghị aka.

N'ụzọ doro anya, nlọghachị ike bụ oge siri ike karị, dịka anyị ga-ahụ, nwere nyocha na-adịghị na-agwọ ọrịa maka ịmepụta mmepe ọgwụ pharmacotherapeutic. Dị ka e gosipụtara Nyocha 1, anyị ga-ekwu okwu na njedebe nke nyochaa nke dabere na nkwụnye akwara nke nlọghachị ịgha azụ dị ka ụdị nhụjuanya siri ike, bụ isi ọrụ nke psychopharmacology na ịgwọ ahụ riri ahụ bụ ịzụlite ọgwụ ndị na-akwalite ịhazi nlọghachi. N'ikwu ya n'ụzọ ọzọ, n'ime ọgwụ ndị kasị baa uru ga-abụ ndị na-akwado ịme mkpebi na-arụsi ọrụ ike, na-ekwe ka onye ahụ nwere ahụike ahọrọ ịghara ịṅụ ọgwụ ahụ. N'ụzọ dị iche, ịmegharị nlọghachị nchịkwa na njikwa mmadụ ma ọ bụ abstinence kachasị mma a na-ejikọta ya na ngwakọta nke ịzụ ahịa ọgwụ na omume omume nke na-akwado ma kwado mkpebi ziri ezi (Centonze et al, 2005). Dịka ọmụmaatụ, mmekọrịta omume nwere ike ịmalite ịmalite nchịkọta dịka ọzụzụ na njedebe na-akpachapụ anya, ịchọta ọrụ na-adịgide adịgide ma ọ bụ ijikọta na ndị ị hụrụ n'anya.

Ọnọdụ nke ịṅụ ọgwụ ọjọọ na nkwụsị nke Ịmụ Ihe Ụgwọ Nhazi

Nyocha 1b gbalịa ịkọwapụta nghọta anyị dị ugbu a banyere ntinye ụgwọ ọrụ ụgwọ ọrụ na usoro ọmụmụ ihe na usoro nke ịṅụ ọgwụ ọjọọ (Kelley, 2004; LaLumiere na Kalivas, 2006). Ya mere, ịchọta ihe ncheta na ịmepụta mmeghachi omume omume na-eme mgbanwe iji nweta ihe ndị dị mkpa dị ka inweta ma kwekọọ na iji ọgwụ ọjọọ eme ihe. Onye ọhụụ na nlọghachị nchịkwa bụ nlọghachite nkwupụta ncheta, ya bụ, ncheta ndị a na-ekwu okwu ma na-eji ha eme mkpebi. N'ikpeazụ, nlọghachị ike nwere ike weere ya dịka ọdịmma ma ọ bụ ncheta usoro. Enweghi ike ikwughachi ihe ncheta usoro, ma na-eduzi mkpochapụ na-enweghị ihe mgbochi nke akpa àgwà ime mgbanwe. Omume ndị a na-amụta nke ọma ma na-arụ ọrụ nke ọma n'enweghị mkpebi ikpe na-aga n'ihu (dịka, na-agba ịnyịnya ígwè, ma ọ bụ na-emeghe ọnụ ụzọ friji mgbe agụụ na-agụ).

Enweela ọganihu buru ibu na afọ iri gara aga na nghọta anyị banyere circuitrị ụbụrụ na ụbụrụ na-arụ ọrụ dị mkpa na-esi enweta ncheta mkpali, na àgwà ndị a mụtara na-egbu. N'ụzọ na-akpali mmasị, ọtụtụ n'ime ihe ọmụma a abịawo site na nchọpụta nchọpụta nchọpụta nke dị n'etiti ndị nchọpụta na-amụ banyere usoro mmezi ihe na-akpali akpali na ndị na-amụ ọgwụ-ọgwụ ọjọọ ahụ dị ka ngwọta na mmụta nkịtị. Nyocha 1b na-egosi otú ụbụrụ ụbụrụ na-ejikọta na ntanetransmitters na nkeji nke ịṅụ ọgwụ ọjọọ. Ya mere, ịmụta ịmalite ịṅụ ọgwụ ọjọọ na-agụnye mkpụrụ ndụ dopamine n'ime mpaghara mmebi (VTA) nke na-ahapụ dopamine n'ime cortex mbụ (PFC), amygdala, na nucleus accumbens (NA) (NA)Berridge na Robinson, 1998; Kelley, 2004; Schultz, 2004; Onye maara ihe, 2004; Jones na Bonci, 2005). Otu usoro ezi uche na-akwado ụdị anụmanụ bụ na ka ndị na-achọ ọgwụ ọjọọ na-amụta nke ọma, ịdabere na omume ndị na-ebute na glutamatergic site na PFC na NA na-apụta (Pierce na Kalivas, 1997; Kadinal na Everitt, 2004; Wolf et al, 2004). Ya mere, nlọghachite nchịkwa na-adabere na nlọghachite nke ncheta ndị metụtara ọgwụ ọjọọ na ntinye nke nkwupụta ncheta ndị a site na njuputa glutamatergic si PFC na NA. Ọ bụ ezie na glutamate nọgidere na-arụ ọrụ kachasị mkpa na nlọghachị nchịkwa na ihe nlereanya a, ntụgharị usoro nke ịmegharị ihe dị iche iche site na nkwupụta ndị ọzọ, ndị nlekọta nke mbụ na-ahụ maka mgbakọ dị iche iche na-agụnye ndị na-emepụta ihe ndị na-emepụta ụgbọala, cortico-striato-thalamic. àgwà ọma a mụtara (Barnes et al, 2005; Everitt na Robbins, 2005).

Ntụle nke a na - agụnye nchịkọta dị omimi nke neuroplasticity nke na - adabere n'ọnọdụ nke ịṅụ ọgwụ ọjọọ, na ijikọta nke a na - enweghị atụ maka ọganihu ọhụrụ maka ọgwụ ndị na - emegharị ahụ site n'ịmanye nlọghachi nchịkwa.

AKWỤKWỌ Ọ BỤ Ọ BỤ Ọ BỤ Ọ BỤ AHỤRỤ ECHICHE

Dị ka e depụtara na Nyocha 1, ugboro ugboro iji ọgwụ ọjọọ eme ihe (iji ọgwụ ọjọọ eme ihe) gụnyere ịmepụ dopamine ugboro ugboro site na mkpụrụ ndụ n'ime VTA n'ime PFC, nke mgbagwoju anya (gụnyere NA), na amygdala. A na-egosipụta circuit a na Nyocha 2a. N'ihe na - emetụta ihe ndị dị ndụ na - akpali akpali, ọgwụ niile na - eri ahụ na - eme ka a hapụ dopamine na mpaghara a, n'agbanyeghị na usoro usoro ihe omimi dị iche iche (Jay, 2003; Kelley, 2004; Nestler, 2005). Mkpakọrịta a n'etiti mmụba nnyefe dopamine na àgwà ịmụta iji nweta ụgwọ ọrụ emeela ka nghọta na nkwụsị nke dopamine bụ ihe dị mkpa iji kwado mmụta. N'ihi ya, ọtụtụ nnyocha na-egosi na igbochi mpempe akwụkwọ dopamine na-ebelata mkpali na mmụta, ebe dopamine na-akpali akpali na-akwalite ịzụlite àgwà mmụta. A na-ekwu na a ga-ahapụ dopamine iji mee ka ihe omume mechie ya na nzụlite, na-emepụta ihe dị n'ime ya na nke a bụ ihe dị mkpa dị mkpa nke na-achọ ịmalite mmeghachi omume (Berridge na Robinson, 1998). Ọdịiche ndị dị mkpa dị n'etiti dopamine nke ọgwụ ọjọọ na-eri vs ihe ndi ozo na-akpali akpali na gburugburu ebe obibi, a na-echekwa mmepe a di oke nkpa maka mmepe nke ichu ogwu.

Nyocha 2b egosi ihe abụọ dị iche iche n'etiti dopamine ntọhapụ na-eso motivational ndu stimuli vs mgbe ị na-ekpughe ọgwụ ọjọọ. Nke mbụ, ntọhapụ nke dopamine site na ọgwụ ọjọọ na-eri ahụ dị ụba na oge karịa enwere ike nweta site na usoro nlezianya. N'ikwu ya n'ụzọ dị mfe, ọgwụ ọgwụ na-eme ka mpempe dopamine na-eme ka mpempe ọgwụ na-adịghị mma site na imeri usoro obibi home na-adịkarị maka ịchịkwa dopamine. Dịka ọmụmaatụ, amphetamine-dị ka psychostimulants na-egbochi mkpochapụ dopamine site na synapses, na n'ọnọdụ ụfọdụ na-akwalite presynaptic dopamine release (Seiden et al, 1993), ebe ọgwụ ndị ọzọ dị ka nicotine ma ọ bụ opioids na-eme ihe iji gbanwee usoro nzaghachị nke sel dopamine, na-eme ka abawanye na ọrụ dopamine cell. N'ihi ya, nicotine na-akwalite ịmịnyefe glutamate na VTA, ebe opioids na-ebelata ọgwụ GABA na-emechi ihe na mpempe dopamine (Nader na van der Kooy, 1997; Laviolette na van der Kooy, 2004; Pierce na Daresan, 2006). Esemokwu dị ukwuu nke abụọ dị na Nyocha 2b n'etiti ọgwụ mgbochi dopamine na-emepụta na nke mepụtara site na ndu nke ndu, bu na inwe ndidi na-ebido iziputa dopamine site na ndu nke ndu, ebe ndi ogwu na-eri mmadu na-etinye dopamine oge obula e weputara ọgwụ. Na ndị ọrụ na-adịghị ala ala, a na-achọ ịba ụba dosing n'ihi nkwụsị, ma iji ọgwụ zuru oke, ọganihu dopamine nwere ike ịdapụta. Ihe ọzọ na-agụnye binges na amphetamine-dị ka psychostimulants, nke nwere ike ime ka mbelata nke dopamine na ndị na-akpali agụụ ọrụ na-adịghị ala ala bụ ndị kọrọ na ọ bụ enweghị ike ịmacha ma ọ bụ ndidi na-eme ka ọrụ ọgwụ ahụ pụta site na usoro ndị a na-amaghị (Martinez et al, 2007). Ya mere, maka ụgwọ ọrụ nke ndụ, ozugbo onye ahụ mụtara àgwà kachasị mma iji nweta ụgwọ ọrụ, nkwụsị dopamine iji mee ka mmụta dịkwuo mkpa adịghị mkpa ma ghara ime (Deutch na Roth, 1990; Schultz, 2004). Otú ọ dị, ọ dị mkpa iburu n'uche na dopamine na-aga n'ihu na-egosi mbata nke nkwụghachi ụgwọ site na nkwalite ọnọdụ (Schultz, 1998). Dịka ọmụmaatụ, ebe inyefe nkwụghachi ụgwọ nri na nzaghachi nwere ike ọ gaghị arụ ọrụ nnyefe dopamine na anụmanụ a zụrụ azụ, ọdịdị nke ihe a na-ejikọta na mbufe nri ga-eme ka dopamine cell na-amịpụta, na-akwadebe ihe anụmanụ ahụ iji malite nri nri nlele nleghachi anya. Ya mere, n'ime usoro nhazi ahụ, dopamine na-arụ ọrụ abụọ, (1) iji mee ka ịmalite ịmalite ịmalite ime mgbanwe na-emetụta ihe ndị dị mkpa, na (2) iji weghachite ozi dị mkpa iji mezue omume omume na-agbanwe agbanwe mgbe ọnọdụ gburugburu ebe obibi kwuru na nri ahụ bụ dị nso. N'ụzọ dị iche, nchịkwa ọ bụla maka ọgwụgwọ ọgwụ ọjọọ na-ejikọta ya na mkpochapụ dị ukwuu nke dopamine nke a ga-atụ anya ịkwalite mmụta ọhụrụ (ya bụ, mkpakọrịta ọhụrụ n'etiti ọgwụ na gburugburu ebe obibi) ma ọ bụ mezuo tupu ịmuta ihe, yana ịkọ onye ahụ na-eri ahụ mebie omume na-achọ ọgwụ ọjọọ (ya bụ nlọghachi). Na ụdị anụmanụ, ihe ngosi nwere ike ime ka mmeghachi omume na-akpali akpali na-emepụta nzaghachi a na-ahụ anya na mkpụrụedemede nke ihe na-akpali akpali. N'ụzọ dị otú a, iji ọgwụ ọjọọ eme ihe ugboro ugboro na-akwalite mkpakọrịta na-arịwanye elu n'etiti ọgwụ ọjọọ na ihe omume ndụ, ebe ọ bụ na ihe ndị dị mkpa na-emetụtaghị ihe dị mkpa. Nke a nwere ike ịkọwa ihe mere eji eji ọgwụ ọjọọ eme ihe na-akpata àgwà ịṅụ ọgwụ ọjọọ iji gbakwunye n'akụkụ niile nke ndụ kwa ụbọchị ka onye ahụ na-adabere.

Dịka e gosipụtara na mbụ, ọgwụ ọjọọ dị iche iche na-eme ka a kwụsị igbu ihe site na usoro dị iche iche. Otu n'ime omume nke ethanol na-arụ ọrụ nke usoro opioid na-esote na ọ bụrụ na ndị na-anabata ndị na-anabata opia na-egbochi site na onye na-emegide ya dị ka naltrexone, mmụba dopamine na-aba n'anya adịghị eme ma ụgwọ a kwụsịrị (Gonzales na Weiss, 1998). Ya mere, ngosipụta nke omume plastik n'ime ụmụ mmadụ nwere ike ịdị iche dị ka ọgwụ ahụ si dị. Dị ka ihe atụ, iji ọgwụ ọjọọ eme ihe na heroin, eji ọgwụ ọjọọ eme ihe na-emepụta akara aka na njiri ihe na-eme ka ndị na -O'Brien, 1975; O'Brien et al, 1977). Ngwọrọgwu ọgwụ ọjọọ na ịṅụ ọgwụ cocaine na-emepụta agụụ na-agụ cocaine na nkwụsị nke limbic (Childress et al, 1999) na njikọta dopamine ejikọtara ya na ya (Volkow et al, 2006). N'ozuzu ya, na ụmụ mmadụ na-eri ahụ, ndidi bụ nkwụsị nke a na-ejikarị hụkarị ọrịa cocaine (O'Brien et al, 2006). Nke a na - ebute ọgwụ ndị na - ejide onwe ha iji nweta ọgwụ ndị e nwetara na mbụ.

Nchọpụta Neuroplasticity nke na-eme ka ahụ ghara ịba uru

D1 na Delta-FosB na-ama ọkwa

Ntọhapụ nke dopamine site na ihe ndị dị mkpa ma ọ bụ ọgwụ ọjọọ riri ahụ na-agbanwe mgbanwe n 'ụbụrụ na-ejikọta ụbụrụ na-eme ka ọ ghara ịdị na-emegharị. Mmetụta nke activation activator dopamine bụ mgbagwoju anya na ọdịiche dị n'etiti mmalite nke D1 vs Ndị na-anabata D2 na-adabere na ọnụnọ nke ebe obibi na tupu postsynaptic n'ime mpaghara elekere nke ebe a nyere. Enwere ọtụtụ nyocha dị mma nke na-akọwa ọnọdụ ọmụma dị ugbu a banyere dopamine na-egosi na ọ na-agụnye ịṅụ ọgwụ ọjọọ na mkpali na-akpali akpali (Berke na Hyman, 2000; Nicola et al, 2000; El-Ghundi, 2007). Maka nzube anyị, Nyocha 3 egosi ihe ụfọdụ mere isi kpọmkwem site na mmalite D1 ntinye aka nke a na-eche dị ka ihe dị mkpa iji mepụta mgbanwe na-adịgide adịgide na physiology na-eme ka mmalite nke omume na-eme mgbanwe na-emetụta ihe ndị dị mkpa, tinyere àgwà ịṅụ ọgwụ ọjọọ. N'ụzọ dị oke mkpa, mkpọsa a na-egosi na-agụnye mgbanwe nke nsụgharị mkpụrụ ndụ na nchịkọta chromatin nke a na-eche na ọ ga-eme ka mgbanwe si n'aka mmadụ na-achịkwa na nlọghachi ike. Ya mere, mkpali nke ndị na-anabata D1 na striatum na cortex na-eme ka cAMP, protein protein protein (PKA) cAMP-dependence, na protein protein-protein (CREB) nke na-akwalite transcript nke ọtụtụ mkpụrụ ndụ na-emetụta ahụ riri ahụ, dịka cfos, deltaFosB, Homer, na preprodynorphin (Hurd na Herkenham, 1993; Nestler et al, 2001; McClung na Nestler, 2003; Benavides na Bibb, 2004). N'ụzọ dị oke mkpa, ịrị elu nke CREB na NA na, ruo n'ókè dị nta, VTA ejikọtara ya na mgbatị ndị a na-eji ọgwụ ọjọọ eme ihe (Carlezon et al, 1998; Nestler, 2005). Ọ bụ ezie na ọ bụghị ọgwụ ọjọọ niile na - eme ka CREB mụbaa na accumbens (Pandey et al, 2004), ikwu okwu nke CREB na ndị na-eme ihe na-egbochi ụgwọ ọrụ nke psychostimulants, na opioids, na ụgwọ ọrụ nke ndụ, ebe nkwupụta nke onye na-ekwu okwu ọjọọ na CREB na-akwalite ụgwọ ọrụ ọgwụgwọ (Barrot et al, 2002; Lu et al, 2003; McClung na Nestler, 2003). N'ụzọ na-akpali mmasị, ụfọdụ nnyocha na-egosi na CREB dị mkpa maka mmetụta na-akwụghachi ụgwọ nke ọgwụ ndị na-eri ahụ na mmụba nke ndụ (Jin et al, 2005; Walters et al, 2005; Choi et al, 2006), na-eme ka o kwe omume na ebe a chọrọ iwu dị oke mkpa nke CREB maka omume ndị kpaliri, ugboro ugboro a na-eme ka CREB na-eme ka mmadụ ghara ịnagide mmetụta ndị na-akwụghachi ụgwọ. Ụfọdụ gọọmenti CREB-achịkwa, dịka preprodynorphin, NAC-1, na Homer, na-atụnye ụtụ na ụba mgbapụta na-emewanye CREB iji belata uru nke ụgwọ ọrụ ọgwụ. Dịka ọmụmaatụ, ụba dynorphin na-egbochi ọrụ nke mkpụrụ ndụ dopamine na ntọhapụ dopamine na presynaptic (Carlezon et al, 1998; Chefer et al, 2000; Hyman et al, 2006), na oganihu okwu nke NAC-1 ma ọ bụ Homer1c n'ime ihe ndị ahụ na-egbochi mmepe nke àgwà ndị a ma ama site na cocaine ugboro ugboro (Mackler et al, 2000; Szumlinski et al, 2006). N'ụzọ dị oke mkpa, abụọ n'ime ndị na-edozi protein, preprodynorphin na NAC-1 na-egosi mmelite nke na-adịgide adịgide na-adịghị mma, na-egosi nkwụsị nke ịkwụ ụgwọ ọgwụgwọ na-adịte aka (Hurd na Herkenham, 1993; cha et al, 1997). O di nwute, dị ka a tụlere n'ụzọ zuru ezu n'okpuru ebe a, nkwụsị ụgwọ ọrụ ọgwụgwọ pụkwara ịgbatị ụgwọ ọrụ ndụ.

N'ime mkpụrụ ndụ nke CREB-achịkwa, mkpụrụbawanye na nchịkwa transcript, deltaFosB, egosipụtawo mmasị dị ukwuu (Nestler et al, 2001). Ọganihu dị n'ọtụtụ ndị na-achịkwa akwụkwọ na mkpụrụ ndụ ndị mbụ site na ọgwụ ndị na-eri ahụ ma ọ bụ ihe mkpali na-akpali akpali, dị ka cfos, Arc, Homer1a, na akwara, na-ebelata mgbe ha gosipụtara ugboro ugboro. N'ụzọ dị iche, deltaFosB na-abanye na ubi dopamine-terminal na cortex na striatum (Nestler et al, 2001; McClung na Nestler, 2003). Nchikota a na - eme nzaghachi nye nchịkwa na - adịghị ala ala nke ọgwụ ọjọọ niile a nwalere n'oge, nakwa dị ka nzaghachi na - akpali akpali ugboro ugboro. Ya mere, nchịkọta nke deltaFosB nwere ike ịdị mkpa maka mmụta na ịzụlite àgwà mkpali n'ozuzu. N'ihe banyere ịṅụ ọgwụ ọjọọ, ịṅụ ọgwụ ma ọ bụ mkpụrụ ndụ ihe ọkpụkpụ nke nsogbu a na-egbochi mmepe nke ụdị ụfọdụ nke plasticity behavioral behavior, such as behavioled motor behaviors (Nestler et al, 2001; McClung na Nestler, 2003). Na mkpụrụ ndụ ihe nketa nke CREB na-achị, ụfọdụ n'ime mkpụrụ ndụ ihe nketa nke deltaFosB na-achịkwa ozugbo nwere ike bụrụ ndị na-akwụ ụgwọ ma jee ozi ịgbachi ọgwụ ike, na ikekwe ịchọrọ ọgwụ (Nestler, 2005). N'ihi ya, ntinye nke Cdk5 phsophorylates nke dopamin-regulated phosphatase DARPP-32, si otú ahụ gbochie phosphorylation na mmalite site na PKA (Benavides na Bibb, 2004). Otú ọ dị, ntinye mkpụrụ ndụ ndị ọzọ site na deltaFosB nwere ike ịkwalite ụgwọ ọgwụ na ihe ka ọtụtụ n'ime nchọpụta na-egosi na nkwupụta nke deltaFosB na-eme ka ụgwọ ọgwụgwọ baa uru (Kelz et al, 1999; Colby et al, 2003; Zachariou et al, 2006). Ihe ntinye nke deltaFosB usoro nke ga-akwalite ụgwọ ọgwụ ọjọọ gụnyere ịmalite GluR2 n'ime shea nke accumbens (Todtenkopf et al, 2006), na ihichapụ okwu nke dynorphin (Zachariou et al, 2006). N'ụzọ dị oke mkpa, ntinye nke deltaFosB na mkpụrụ ndụ nke mkpụrụ ya na-achịkwa na-egosi na ọ dịtụghị agafe agafe ma na-ahazi n'oge abstinence. Ya mere, ọ bụ ezie na ọ dị mkpa maka ịzụlite àgwà ịṅụ ọgwụ ọjọọ, deltaFosB n'onwe ya abụghị ihe atụ nke neuroplasticity nke na-edozi ọgwụ na-edozi ahụ nke na-etinye aka n'ịgbasa usoro nchịkwa ma ọ bụ ịmaliteghachi ike. N'ezie, ọ bụ ọdịdị nke deltaFosB okwu nke na - eme ka ọ bụrụ ezigbo onye na - akwado maka protin na - emegharị ntụgharị site na mmekọrịta mmadụ na -Nestler et al, 2001). Ya mere, ebe deltaFosB a na-achịkwa usoro okwu onwe ya na-agbanwe agbanwe, usoro nchịkwa nke mkpụrụ ndụ ndị a na-achịkwa nwere ike bụrụ nke siri ike n'oge abstinence. Dịka ọmụmaatụ, enwere ọganihu na-adịgide adịgide na njupụta nkwụsị nke dentritic ka a kọọrọ na mkpụrụ ndụ spiny acumbens n'oge abstinence abughi nke sitere na chronic psychostimulant administration (Robinson na Kolb, 2004), na mmụba a na-agbasa na akụkụ site na deltaFosB mmalite nke Cdk5 (Norrholm et al, 2003).

Na nchịkọta, ntinye akara nke D1, CREB, na deltaFosB na-egosi na ọ dị mkpa maka ịkwọ ụgbọala neuroplasticity bụ nke na-adabere na nkuzi na-akpali akpali na ịzụlite àgwà ịṅụ ọgwụ ọjọọ (na-Nestler, 2001; Hyman et al, 2006). Otú ọ dị, ọrụ maka mmegharị ọgwụ na-emetụta ọgwụ ọjọọ na nke a na-egbu ọgwụ ma ọ bụ na-enweghị ike ịlọghachi bụ ihe mgbagwoju anya. Dịka ọmụmaatụ, ọhụụ na-adịte aka ma na-adịgide adịgide kpatara site na ịbanye CREB ka egosipụtakarị na ọ ga-arụ ọrụ ọrụ iji belata dopamine ma ọ bụ ịmịnye glutamate na accumbens, ebe ọnụ ọgụgụ deltaFosB na-achịkwa okwu mkpụrụ okwu n'ụzọ dị mma (mụbaa Cdk5 ) ma kwado ụgwọ ọrụ ọgwụgwọ (mụbaa GluR2; dynorphin belata). Mgbanwe ndị a n'ozuzu ga-ebelata uru dị mkpụmkpụ nke mkpali na-akpali akpali, nke a pụkwara inye aka na-enwe nsogbu na-adịgide adịgide iji laghachi azụ n'ịchọ ọgwụ ọjọọ. Ya mere, site n'iji arụ ọrụ na-akwụ ụgwọ iji gbanwee ụgwọ niile, njigide ngwongwo na-adịgide adịgide nke njedebe transitory nke D1-CREB (eg, mụbaa dynorphin, NAC1, na Homer1c) na-akwalite ọgwụ na-achọ inweta inweta ụgwọ ọrụ ndụ.

Ụbụrụ Neurotrophic Factor nke Ụbụrụ na-esi na ya apụta na ịṅụ ọgwụ ọjọọ

Mgbanwe ọzọ nke dopamine na-adabere na njikọ protein bụ nke gosipụtara na ọ dị mkpa ka e guzobe usoro ọgwụgwọ nakwa usoro nkwụplasticity na-emetụta ọgwụ ọjọọ na-ebili na ụbụrụ na-ahụ maka ụbụrụ (BDNF). BDNF nọ na klas nke psychostimulant-na-achịkwa mkpụrụ ndụ ihe mmalite oge mbụ, gụnyere Arc, c-fos, na zif / 268 (Dunais na McGinty, 1994; Moratalla et al, 1996). Otú ọ dị, BDNF na Arc dị iche iche n'ihi na mRNA dị ike na-ebugharị ma na-ebuga dendrites site na arụ ọrụ cellular (Steward and Worley, 2001). Maka otu mmasị, ma o doro anya na ọ dị iche na mkpụrụ ndụ nke deltaFosB na-achị, yana mkpụrụ ndụ ndị ọzọ na-arụ ọrụ site na psychostimulants, mgbanwe ndị na-adịgide adịgide na BDNF na-ejikọta na oge ụba abstinence (Grimm et al, 2003; Lu et al, 2004a; Filip et al, 2006). Ọzọkwa, ndị BDNF na-akpali akpali na amygdala, NA, ma ọ bụ VTA na-akwalite (Horger et al, 1999; Lu et al, 2004b; Graham et al, 2007; Pu et al, 2006), ebe microinjection nke BDNF n'ime PFC na - egbochi ịchọrọ ọgwụ (Berglind et al, 2007), na-egosi na ịkwalite nke deltaFosB, BDNF na-arụ ọrụ nchịkọta dị iche iche n'ịkwado neuroplasticity nke ọgwụ ọjọọ ji eme ihe iji mezie nlọghachi iwu na ịmanye.

A maara nke ọma BDNF iji kwalite ụdị nke plastia synaptic, dịka mmalite nke oge na-egbu oge (LTP), na-akwalitekwa usoro nkedo nke dendritic (Bramham na Messaoudi, 2005). Usoro ndị na - akpata ihe dị n'ozuzu ka mmelite na ntinye aka dị iche iche dịgasị iche iche, na - agụnye ịba ụba synaptic vesicle, ịmalite ịba ụba glutamate, na ịkwalite NMDA postsynaptic. N'ibunye usoro ndị a, ọ bụghị ihe mgbagwoju anya na BDNF etinyewo aka na nkwụnyeghị ihe na-emetụta usoro ọmụmụ na usoro nchekwa. Banyere ọgwụ ọjọọ riri ahụ, BDNF na-egbochi nkwụsịtụ na-adịgide adịgide nke nnyefe nnyefe na mkpụrụ ndụ dopamine n'ime VTA nke a na-enweta site na nchịkwa cocaine ugboro ugboro (Pu et al, 2006), nakwa na ntọhapụ orexin (Borgland et al, 2006), nwere ike itinye aka na ntinye egwu nke LTP nwere ike na VTA nke na-eso otu nchịkwa nke ọgwụ na-eri ahụ (maka nyochaa ihe ndị a na otu ha ga - esi mee ka mmepụta nke ụdị neuroplasticity na - adịgide adịgide nke na - Jones na Bonci, 2005). N'ụzọ dị oke mkpa, ọkwa nke BDNF na VTA, yana NA na amygdala, na - arịwanye elu n'oge abstinence (Grimm et al, 2003). A na-atụle mmụba ọganihu a na-enwe ọganihu iji mee ka mmụba na-arịwanye elu na-achọ ọgwụ ọjọọ nke na-eme mgbe a na-ewepụ cocaine, nke nwere ike ime, n'otu akụkụ, site na ịmalite okwu ntinye nke dopamine D3 (Guillin et al, 2001; Le Foll et al, 2005). Eziokwu ahụ bụ na nnukwu ụlọ ọgwụ na-ebuli BDNF ma na-anọgide na-ebuli elu na mpaghara ụbụrụ ụfọdụ mgbe abstinence gosipụtara na protein a dị ka onye na-edozi neuroplasticity siri ike bụ nke nwere ike inye aka na ịchọta ọgwụ na-achọ ọgwụ, na nyocha nke ịchọ ọgwụ ọjọọ oge abstinence.

Neuroplasticity nke na-agagharị agagharị na-ejikọta na Ngalaba Molecular nke Ọgwụ Ọjọọ

A kọwakwara ụdị ọrịa ụfọdụ na-adịghị agbanwe agbanwe bụ ndị na-eji ọgwụ ọjọọ eme ihe. Otú ọ dị, n'adịghị ka ụzọ mgbaàmà D1-CREB-deltaFosB, ihe ndị a na-egosi na ọ bụ kpọmkwem ọgwụ ndị mmadụ. Dịka ọmụmaatụ, mgbanwe ndị transporters na-ejikọta na amphetamine-dị ka psychostimulants (Daws et al, 2002), GABA-A gbanwee mgbanwe ndị nabatara mgbe mmanya na-adịghị ala ala (Charlton et al, 1997), na nicotine na-eme ka ndị nicotinic ndị natara (Mansvelder na McGehee, 2000). Mgbanwe ndị a na-eme ka ọgwụ na-eme ka ọ bụrụ ọgwụ ọjọọ na ọgwụ ọjọọ ọ bụla, karịsịa, syndromes nke mwepụ nwere ihe pụrụ iche maka klas ọ bụla. Ọzọkwa, mgbanwe ndị ọgwụ ọjọọ na-eme ka ndị na-arụ ọrụ circuitry dị mkpa maka ụgwọ ọrụ nkịtị na ịṅụ ọgwụ ọjọọ. N'ikpeazụ, ihe ndị na-eme ka ịṅụ ọgwụ na-agabigaghị nchịkọta nke nyocha ugbu a bụ nke na-elekwasị anya na ihe yiri ka ọ bụ ọdịdị nke ụbụrụ nke ụbụrụ nke ọtụtụ ma ọ bụ ọgwụ ọjọọ niile na-emekọ, na-emetụtakwara na mkpali na-akpali akpali.

Nchịkọta nke Neuroplasticity nke na-egosi na ịṅụ ọgwụ ọjọọ na mgbanwe nke si n'aka Ọgwụ Nlekọta Ahụike na-achịkwa.

Nyocha 4 na-egosipụta ọdịdị anụ ahụ dị iche iche nke anụ ahụ na-adịghị na nchịplasticity na-ejikọta iji ọgwụ ọjọọ eme ihe ugboro ugboro na abstinence n'ọdịnihu. Ọ dị mkpa iburu n'uche na nnwale ndị a na-eme na ugboro ugboro psychostimulant ochichi, nakwa na ọ dị ntakịrị ogo opioids, na-enye ọtụtụ ihe ọmụma na-adabere n'ụkpụrụ e gosipụtara na Nyocha 4a. A na-atụle izu ụka atọ. Akụkụ mbụ na-agụnye ịmalite mkpụrụ ndụ nke ọrụ site na nnukwu nlekọta, na mmepe nke ndidi na ntinye a na-esote nchịkwa ugboro ugboro. Ndị na-edozi na mpaghara a gụnyere c-fos, Arc, Homer1a, narp, na zif / 268. N'ụzọ dị oke mkpa, na-esochi oge nke abstinence, nkwado na-agbadata ma ndị na-edozi protein a ọzọ nwere ike ịmalite ọzọ site na nnukwu ọgwụgwọ psychostimulant, mgbe mgbe n'ọtụtụ ma ọ bụ na usoro nke okwu dị iche na nke ahụ na-ebute site na mbụ ọgwụ. A na-eche na ndị a na-edozi ahụ dị oke egwu maka ịmalite ịmịnye neuroplasticity dị mkpa iji nweta àgwà ọhụrụ, yana iweghachite àgwà amụta, gụnyere ịchọrọ ọgwụ.

Akụkụ nke abụọ bụ ndị na-edozi ahụ nke okwu ya ji nwayọọ nwayọọ na-abawanye ma ọ bụ na-ebelata site na iji ọgwụ ọjọọ eme ihe ugboro ugboro, ma na-echere oge dị iche iche nke abstinence. E gosipụtara mpaghara abụọ dị na ya Nyocha 4b. Nke mbụ na-agụnye mgbanwe protein nke na-adịgide ruo ọtụtụ awa ruo ụbọchị ruo na ịinụbiga mmanya ókè ma na-adaba na mgbanwe ndị nwere njikọ chiri anya na saịtị nke ọgwụ ọgwụ. Akụkụ nke ọzọ bụ nke nchịkọta deltaFosB, bụ ebe ọkwa dị elu nwere ike ịtachi obi ruo ụbọchị ma ọ bụ izu. A na-eche na ngalaba nke ikpeazụ a ga-enye aka inweta nnabata nke mmụta, mana ọ dị mkpa, na nzaghachi maka ị toụ ọgwụ ọjọọ ugboro ugboro, a na-eche deltaFosB iji gbasaa ntụgharị maka iji ọgwụ ọjọọ eme ihe iji weghachite ojiji (Nestler, 2005).

Ụdị nke atọ nwere protein na-ebuli ma ọ bụ belata mgbe abstinence ogologo oge. A na-atụle mpaghara abụọ dị na ya Nyocha 4c. Nke mbụ bu BDNF na-egosi ya nke na - agbakọta na mpaghara ụfọdụ ụbụrụ mgbe ọchịagha psychostimulant ugboro ugboro na nzụlite a na - eto eto na - arịwanye elu oge nke abstinence (Grimm et al, 2003; Lu et al, 2004a). A ga-atụle nkebi nke abụọ na nkowa n'okpuru, ma nwere protein ndị na-adịghị agbanwe agbanwe n'oge a na-achịkwa ọgwụ, ma a na-ebuli elu ma ọ bụ belata n'oge abstinence. A na-eche na ụdị a nwere ihe ndị na-adịghị mma na-eme ka ọ ghara ịghaghachi azụ. Imirikiti mgbanwe ndị a na-adịgide adịgide egosighi na ọ ga-eme na nzaghachi na nkwupụta ugboro ugboro na ihe ndị na-akpali akpali nke ndụ ma nwee ike bụrụ ndị na-ahụ maka ihe ndị na-agwọ ọrịa.

ỊNỌDỤ NDỊ NA-AGBANYERE Ọ BỤ EKPERE MGBE ỌZỌ BỤ EZIOKWU

Dị ka akọwara n'elu, otu omume a haziri iji nweta ụgwọ ọrụ ma ọ bụ zere mmerụ ọjọọ, ọrụ nke dopamine na-agbanwe site na otu nke na-akwalite mmụta ọhụrụ iji mee ka iji ihe ọmụma mụtara mee ihe n'ụzọ dị irè iji mezue mmeghachi omume omume mgbanwe (Schultz, 2004). N'ụzọ dị iche, ịmịnye glutamate site na cortex na allocortex (dịka, amygdala na hippocampus) n'ime njem ụgbọ okporo ígwè (gụnyere NA) pụta dị oke nkpa maka ime ihe mmụta (Kalivas na Volkow, 2005). Ọzọkwa, a na-eche na dịka a na-emeghachi omume ugboro ugboro, ọrụ nke glutamate nke na-asọpụta site na PFC na amygdala n'ime NA, aghọghị ihe dị mkpa maka mmụba glutamate na-esi na ọdụ ụgbọ mmiri na-eme njem na steeti (Everitt na Robbins, 2005). N'ụzọ dị otú a, omume na-agbanwe site n'ịdị na-akọwa usoro metụtara ọrụ nlekọta mbụ na-eji arụ ọrụ eji arụ ọrụ na-arụ ọrụ (Barnes et al, 2005). N'ihe gbasara ahụ anya, mgbanwe a site na nkwupụta na omume akpaaka nwere ike ime mgbanwe site na ikwe ka omume ndị a mụtara nke ọma ka ha gaa n'ihu na-enweghị ihe ọ bụla, ọ bụrụ na ihe mkpali dị mkpa ma ọ bụ ihe gbanwere, ọrụ nchịkwa na-amalite imebi omume ahụ dịka akụkụ nke ịmepụta mmegharị omume ọhụrụ ekwesiri ime mgbanwe gburugburu ebe obibi. N'ihe banyere ịṅụ ọgwụ ọjọọ, mgbanwe a site na ntinye nke mbido iji rụọ ọrụ eletrik moto na-egosi nkwụsị nke nchịkwa na nlọghachi ike. Ihe dị mkpa maka ụdị ọgwụgwọ ahụ, ikike nke ibu ụzọ, ikwupụta sekit maka ịmalite ma mebie ụdị ọchịchọ ịṅụ ọgwụ ọjọọ, na-eme ka ọ siere mkpebi mkpebi oke ike ịbanye na ịchọrọ ọgwụ (Everitt na Robbins, 2005; Kalivas na Volkow, 2005). Ịghọta neurophysiology nke na-eme ka mgbanwe a na-adịghị mma na-eme ka ịchọọ ọgwụ ọjọọ na-achọ, na nhụsianya nke ịmalite ịchịkwa ịchọrọ ọgwụ ọjọọ na-achọ ịghọta ngụkọta neuroplasticity cellular na-adịgide adịgide na-eji ọgwụ ọjọọ eme ihe ugboro ugboro. Karịsịa, nke a na-agụnye ịchọta mgbanwe nke nnyefe glutamate na ntoputa nke hypofrontality nke na-ekwe ka ịṅụ ọgwụ na-aga n'ihu n'emeghị ihe ọ bụla (Jentsch na Taylor, 1999; Goldstein na Volkow, 2002).

Nkwụsị Neuroplasticity Na Cortical Glutamate Circuitry: Human Neuroimaging

A na-ahụ ọtụtụ ihe ndị na-adịghị ahụkebe na cortical circuits n'ụzọ doro anya na ọgwụ ndị na-eri ahụ site n'iji ụzọ dịgasị iche iche na-agwọ ọrịa. N'ihi ya, a na - eme ka ọnụ ọgụgụ zuru ezu nke usoro mgbochi nke metabolism cellular na ọbara na - esi na ndị mmadụ na - aṅụ ọgwụ dịgasị iche iche, sitere na cocaine na -Goldstein na Volkow, 2002). Nke a na-agụnye ógbè dị iche iche dịka ikuku na-emepụta ma ọ bụ ikuku na-agba ume. N'iburu njikọ dị n'etiti ịme ka ọkpụkpụ azụ na-arụ ọrụ ma na-etinye àgwà dị mkparịta ụka na-akpali akpali (na-akpali akpali)Na-emegharị et al, 2002), na n'etiti mmalite nke cortex na-agba ume ma ọ bụ na-enwe ike ịgbanwe àgwà a na-amụta nke ọma na omume mmegharị ọhụrụ (Kolb et al, 2004), a na-akọwa ụdị hypofrontality a dị ka njigide siri ike nke ebelata ikike ịhazi ọgwụ ọjọọ. A kọwakwara mkpịsị ụkwụ ndị na-adịghị mma na-aṅụ ọgwụ na-eri ọgwụ (Franklin et al, 2002), ma amataghi ma ihe ndị a na-egosi na ha bụ hypofrontality bụ ihe ndị na-adịghị mfe tupu ha enwee ike iji cocaine ma ọ bụ mmetụta nke iji ihe na-akpali akpali. N'ụzọ na-adọrọ mmasị, mgbe a na-ekpughe ihe a na-ejikọta na ọgwụ ọjọọ nke na-ebute ọchịchọ maka ọgwụ ọjọọ, a na-eme ka a malite ọrụ na PFC, gụnyere ịgba aghara na ikuku na-emepụta (orbital cortices)Goldstein na Volkow, 2002; Wilson et al, 2004; Kalivas na Volkow, 2005). N'ọtụtụ ọmụmụ, arụ ọrụ dị na PFC ejiriwo nke ọma jikọta ya na ike nke ọchịchọ na-emetụta ya maka ọgwụ ahụ. Ya mere, ọdịiche dị n'etiti ọrụ mbụ n'etiti isi ihe na ọkwa dị iche iche nke mkpokọta ọgwụ dị elu karịrị ihe na-eme na njikwa ihe na-eme ka a zaaghachi na nzaghachi ndị e jikọtara ya na ụgwọ ọrụ ndụ, dị ka mmepụta ihe anya nke mmekọahụ. Ozokwa, a na-ejikọta ihe jikọrọ ya na iri ahụ site na nzaghachi nzaghachi nye ụgwọ ọrụ nke ndụ, mgbe a na-etinye ihe oriri nke na-eri cocaine na ihe mkpali agụụ mmekọahụ, mmalite nke mbido na-enwechaghị nsogbu ma ọ bụrụ na e jiri ya tụnyere njikwa (Garavan et al, 2000). Mgbalị ndị a na-eme iji guzogide ọchịchọ na-agụsi agụụ ike maka nzaghachi nke cocaine ekwupụtakwala ka mmụba na-aga n'ihu n'ihu (Childress et al, 2007), na-atụ aro na arụrụ ọrụ ahụ rụrụ arụ nwere ike ime ka ọ ghara inwe ike iguzogide nlọghachi.

Ihe ọzọ na-achọpụta site na nchọpụta na-emegharị anya na-egosi nzaghachi nke nzaghachi na nkwụsị nke ndụ na-eri ahụ bụ nbelata nzaghachi nke ntinye ọgwụ dopamine na nzaghachi nke psychostimulants (Volkow et al, 2004, 2005). Ya mere, methylphenidate na-ebunye dopamine ntọhapụ n'ime striatum na enweghi nsogbu na ndi na-eri cocaine nke na-ejide ya. Ọzọkwa, n'agbanyeghị ụdị ọgwụ ọjọọ kachasị njọ, ndị na-eri ahụ na-egosi na ndị D2 na-anabata ihe na striatum (Volkow et al, 2004). Dịka ndị natara D2 belatara na-egosi ọnyà dopamine, ọ bụghị ihe mgbagwoju anya na akụkọ nchịkọta akụkọ na-ebelata ma ọ bụ obi ụtọ na nzaghachi na methylphenidate metụtara ịchịkwa isiokwu. N'ụzọ dị iche, ebe methylphenidate na-adọta ọchịchọ siri ike n'ime ndị ahụ riri ahụ, enweghi agụụ na-atụle ihe ndị metụtara ya. Otú ọ dị, ndị na-aṅụ ọgwụ na-ejikwa akara achị dịgasị iche dịka nkwụsị ntanye nke D2 ha. Ndị nwere ọnụ ala D2 dị ala dị mma, mmetụta na-enye obi ụtọ site na methylphenidate, ebe ndị nwere ogo D2 dị elu adịghị amasị mmetụta nke stimulant (Volkow et al, 2002). Nchọta a na ihe ndị mmadụ na-ahụkarị yiri nke nchọta yiri nke ahụ na primates na-abụghị ndị mmadụ (Nader na Czoty, 2005).

N'ịkọkọta ọnụ, nchọpụta ndị a na-eme ka ọ ghara ịdị na-egosi mgbanwe na mesocorticolimbic circuitry. Ya mere, na mpaghara nchịkwa, onye ahụ na-eri ahụ dịka ọ na-emetụta ihe ndị na-akpali akpali na-akpata, dị ka ọhụụ na-egosi na ọ bụ mmadụ abụọ, (1) belatatara ọrụ na PFC, na (2) nke na-eme ka ndị na-anabata dopamine D2 natara. Ikekwe ọbụna ihe dị oké egwu banyere ụdị ọrịa ahụ riri ahụ, ikike nke ihe ndị dị mkpa iji mee ka PFC kwụsị ọrụ. N'otu aka ahụ, a na-emepụta ọgwụ dopamine na striatum na ọgwụ na-eme ka ọgwụ na-emetụta ya. Otú ọ dị, ihe ndị metụtara ọgwụ ọjọọ na-eme ka PFC rụọ ọrụ n'ụzọ ọgwụ ọjọọ na-ejikọta ya na ọgwụ ọjọọ. N'ịkọtara ọnụ, data ndị a na-adịghị egbochi na-enye usoro nchịkwa nke neurocircuitry maka ọdịdị kachasị nke ahụ riri ahụ; oke, ịghara ịjụ ọgwụ maka ọgwụ ọjọọ, ma ọ bụ ndị dara ogbenye ma ọ bụ ndị na-ekwesịghị ekwesị na-aza maka ihe ndị dị mkpa.

Ịkwụsị Neuroplasticity na Cortical Glutamate Circuitry: Ụdị anụmanụ

Iji ghọta ntọala cellular maka otú mgbanwe ndị a na corticolimbic circuitry si eme ma nwee olileanya iji chọpụta usoro maka ịgbanwe ma ọ bụ na-agbanwe mgbanwe ndị ahụ, ọ dị mkpa iji ụdị anụmanụ, nke na-enye ohere iji nyochakwu usoro. N'ụzọ dị oke mkpa, ụmụ anụmanụ na-edozi ọgwụ ndị na-eri ahụ ụmụ mmadụ, na mgbanwe nke sekit site na ntinye ọgwụ dopamin-nkwado nke ịchọrọ ọgwụ na-egbu egbu nke ịchọrọ ọgwụ ọjọọ pụtara ìhè na ọmụmụ ụmụ anụmanụ.

Ụdị nlọghachị kachasị n'ọrụ nke nlọghachị gụnyere agụmakwụkwọ ọzụzụ iji nye onwe ya ọgwụ, itinye anụ ahụ na mmanye mmanye ma ọ bụ ma ọ bụ na-enweghị nkuzi mkpochapu, ma weghachite ụmụ anụmanụ na ọnọdụ ọgwụ ọjọọ, amaokwu nke jikọrọ aka na ịṅụ ọgwụ ọjọọ, nrụgide maọbụ ọgwụ ọjọọ ahụ (Epstein et al, 2006). Na nzaghachi na ihe ndị a, anụmanụ a zụrụ ọgwụ ga-etinye aka na ọgwụ ọjọọ ọbụna ma ọ bụrụ na enweghị ọgwụ.

Ntụle ọmụmụ banyere nlọghachi n'ime ụmụ anụmanụ na-agụnye iji rats na-arụ ọrụ na naloxone ma ọ bụ naltrexone. Akwụsịrị ụgwọ ọrụ opiate na mgbe mbido mbido mụbaa, mmepe ngwa ngwa mere (Davis na Smith, 1974). N'oge na-adịbeghị anya, achọtara onwe onye nlekọta mmanya na-eme ka usoro opioid dị ọhụrụ na-emepụta ntọala dopamine na NA na mmanya na-achọ anụ ahụ (Gonzales na Weiss, 1998). Rats a zụrụ azụ na ịṅụ mmanya na-enye onwe ya ma nyezie naltrexone ga-egosi na cessation nke dopamine abawanye na NA na ịkwụsị nke mmanya na-elekọta onwe. Nlereanya a na-ehichapụ anya na-emetụta na ndị aṅụrụma na-akọ na ụgwọ ọrụ mmanya na-abawanye ma ọ bụ na-adịghị enweta mgbe a na-emeso ya na naltrexone (Volpicelli et al, 1995).

N'oge na-adịbeghị anya, ịmalite imechi ụbụrụ nke ụbụrụ dị iche iche na agba ma ọ bụ ogige GABA na-egbochi ime ihe omume, ụbụrụ ụbụrụ dị mkpa iji kpochapụ ọgwụ ọjọọ achọpụtala (McFarland na Kalivas, 2001; Hụ, 2002; McFarland et al, 2004). Ihe nchoputa nke omumu ndia mere n'ime iri afo gara aga bu ihe ndi ozo dika ihe ndi mmadu kwuru. Dorsolateral striatum bụ mpaghara ụbụrụ nke egosiri na ọ bụ iwu ọ bụla n'agbanyeghi ụdị ọnọdụ maka ịmalite ịchọrọ ọgwụ, ma ọ bụ nkwenye ma ọ bụ enweghị nkuzi mkpochapu. Nke a na-egosipụta nsonye nke ime njem sekit na-eme nke ọma n'omume a zụrụ azụ dịka ịchọrọ ọgwụ. N'ụzọ dị ịtụnanya, ọ gwụla ma ụmụ anụmanụ na-aga ịnwụcha ọzụzụ, a naghị emetụta ọgwụ ọjọọ a na-etinye site n'ime ka ụmụ anụmanụ laghachi na ọgwụ ọjọọ na-egbochi ụbụrụ ụbụrụ ọ bụla jikọrọ ya na mkpali kpaliri ma ọ bụ ịmalite inwe ọmụmụ ihe na-adịghị emetụta ihe gbasara ahụike (dịka, ebe nke PFC, amygdala, ma ọ bụ NA) (Fuchs et al, 2006). Otú ọ dị, ọ bụrụ na anụmanụ ahụ na-enweta ọzụzụ na-ekpochapu, ịchọrọ ọgwụ ọjọọ site na njide, nchekasị, ma ọ bụ ọgwụ n'onwe ya na-eme njem eletrik dịkwuo ụtọ, nke nwere circuitry nke a kọwara na ụmụ mmadụ na-eri ahụ. Dịka ọmụmaatụ, ọ bụrụ na onye na-eme nchọpụta na mpaghara na-egbochi nke ọ bụla n'ime ihe ntanetị na usoro usoro nke nwere profaịlụ dopamine si VTA gaa na PFC dorsal, mgbagharị glutamate sitere na PFC na NA ma ọ bụ GABA / peptide projection si accumbens na ventral pallidum (VP), a na-egbochi anwụrụ ọgwụ na anụmanụ emenyụrụ. Ya mere, nkuzi mkpochapu na-eme ka akụkụ ụbụrụ na-etinye aka n'ịkwalite nkwupụta na mmetụta uche n'ime omume ọgwụ ọjọọ (McFarland na Kalivas, 2001; Hụ, 2002; McFarland et al, 2004), nke na-egosipụta nkwenye nke usoro mgbanwe omume. Dika mkpochapu ọzụzụ na-eweta nduzi omume, ọnụ ọgụgụ nke ịṅụ ọgwụ ọjọọ (dịka, ịpị ọkụ ọkụ) nke usoro ọgwụ ọjọọ na-ejupụta na ụmụ anụmanụ dị oke elu dị elu karịa ọgwụ ndị a na-enwupụta na ụmụ anụmanụ na-emenyụ emenyụ (Fuchs et al, 2006). Otu, data sekit na nke omume na-egosi na ikirikiri sekit ndị jikọtara ọnụ na ịṅụ ọgwụ na ihe ndị a na-emenyụ emetụta na-eme ka ịchọọ ọgwụ. Nkwado nke a, ọzụzụ na-ekpochapu GluR1 na GluR2 glutamate na-anabata ihe na NA nke azụ anụ (cocaine)Sutton et al, 2003). N'otu aka ahụ, nkuzi mkpochapu n'ime ụmụ anụmanụ na-atụ egwu gụnyere ịmalite nke cortex infralimbic na-arụ ọrụ na NA (Sierra-Mercado et al, 2006). Ya mere, dị ka mmekorita nke psychosocial na ụmụ mmadụ na-agbalị ịmaliteghachi ọrụ nchịkwa na-achọ ọgwụ ọjọọ, nkuzi na-ekpochapu ụmụ anụmanụ na-eme njem dị n'ihu nke bara uru nke na-agbanwe usoro ọgwụ ahụ na nzaghachi, nchekasị, ma ọ bụ ọgwụ n'onwe ya.

A na-egosiputa ihe dị iche iche dị iche iche n'etiti ụmụ anụmanụ na-agwọ ọrịa na ụmụ mmadụ na-aṅụ ọgwụ ọjọọ ahụ site na nrịba ama dị ịrịba ama na ịmịnye glutamate mgbe ịchọrọ ọgwụ ọjọọ. Ya mere, oke a zụrụ azụ na cocaine onwe ya ma ọ bụ heroin na-egosi mmụba dị ịrịba ama na synaptic glutamate ntọhapụ na NA na nzaghachi maka ịṅụ ọgwụ ọjọọ ma ọ bụ nrụgide-ịmalite ịchọrọ ọgwụ (McFarland et al, 2003, 2004). Ọzọkwa, a kwụsịrị ịrị elu a site na mgbochi nke PFC dorsal, ọ dịghịkwa na nnu saline ma ọ bụ cocaine na-ejikọta ya ma ọ bụ ìgwè ndị na-achịkwa heroin. N'ikwu ya n'ụzọ ọzọ, n'agbanyeghị usoro nchịkọta ọgwụ ọjọọ ugboro ugboro, ọ bụrụ na ụmụ anụmanụ adịghị etinye aka n'omume ọgwụ ọjọọ, a gaghị ahapụ synaptic glutamate nke dysregulated. N'ihi ya, nnukwu ọgwụ nchịkwa naanị ezughị iji rụọ ọrụ ụzọ mgbochi mbu, kama nke a, ụmụ anụmanụ na-amụta ọrụ na-achọ ọgwụ. N'ụzọ dị oke mkpa, enweghi ọganihu na glutamate mgbe a na-achọ ụmụ anụmanụ ndị a zụrụ azụ iji nweta nri nke onwe ha, na-egosi na ọ bụghị ihe mgbochi a na-adọta site n'ịmụta ịchọta ụgwọ ọrụ ndụ (McFarland et al, 2003). Na-akwado mkpa nke dysregulation na njuputa glutamate na ịkwọ ụgbọala na-achọ ịṅụ ọgwụ, nnweta na-ejide onwe ya nke ndị na-achọ ịṅụ ọgwụ ọjọọ na-egbochi ọgwụ na-achọ, dịka ọ na-adịghị arụ ọrụ nke PFC (Cornish na Kalivas, 2000; Di Ciano na Everitt, 2001). N'oge na-adịbeghị anya, a na-amụ ihe ụfọdụ n'ime neuroplasticity nke na-eme nchọpụta nke na-ekwusara ihe gbasara mgbagwoju anya nke na-egosi na ị na-amụ ihe. Tụkwasị na nke ahụ, a na-enyocha ụfọdụ ihe na-esi na nkwụsị nke ịṅụbiga mmanya ókè mgbe a na-achọ ọgwụ ọjọọ.

Neuroplasticity na-enye aka na Transmission Glutamate Dysregulated

Dika ntughari nke oke glutamate na-enwe ntachi obi, ihe kwekọrọ na molecular plasticity na-atachi obi. Ihe kachasị dị n'etiti mgbanwe ndị a na-eme ka ikpo okwu ndị a bụ modregulation nke mgbanwe cystine-glutamate (xc-) (Baker et al, 2003). xc- bụ nkwụsịtụ nke na-eme ka ọnụ ọgụgụ nke mkpụrụ ndụ nweta cystine iji mee ka nkwonkwo antioxidant intracellular, ma na -eme site na-agbanwe mgbanwe nke otu cystine iji gbanwere maka otu mpempe akwụkwọ nke glutamate intracellular n'ime oghere extracellular (McBean, 2002). Dị ka ọ dịkarị, nsụgharị glutamate a na-enweghị isi na-eweta ọkwa dị na ohere extracellular zuru ezu iji kpalie mpempe akwụkwọ na-emepụta ihe ndị na-emepụta ihe na-edozi ahụ (mGluR), nke na - eme ka a kwụsị synaptic glutamate release (Moran et al, 2005). Otú ọ dị, belata x nke na NA mgbe cocaine na-adịghị ala ala na-ewepu ihe a na-egbochi tonic, na-enwewanye ihe ịga nke ọma synaptic glutamate. A na - ejikọta ụda a na ụda dị ala site na mGluR prynaptic, nke a na - eche na ọ ga - eme ka ụba phosphorylation na -Xi et al, 2002), na induction nke protein a na-akpọ onye ọrụ GN protein na-egosi 3 (AGS3), nke na-eme ka njedebe nke ihe nkwụnye ihe ngosi site na Giα klas nke protein G (Blumer na Lanier, 2003; Ụda et al, 2004; Yao et al, 2005). E gosipụtara mmekọrịta a Nyocha 5.

A na-eche na ịhapụ sylịptic glutamate ugboro ugboro mgbe a na-achọ ịchọrọ ọgwụ ọjọọ ugboro ugboro na-eme ka ọtụtụ mgbanwe mgbanwe postsynaptic na-adịgide adịgide. Nke kachasị n'etiti ndị a bụ mgbanwe ndị dị mma na nrịjuanya spine dendritic nke a hụrụ na NA na ebe ndị na-aga n'ihu n'ihu mgbe ha nyesịrị ọgwụ ugboro ugboro na ọgwụ ọjọọ (Robinson na Kolb, 2004). Ekwadoro nke ọma na itinye glutamate n'ahịrị na omenala na-agbanwe mmụkpụ azụ, ma ọ bụ na-abawanye ma ọ bụ na-ebelata dabere na ọnụọgụ mmịnye glutamate na-akpali akpali na ikekwe subtypes kpaliri (Lippman na Dunaevsky, 2005; Richards et al, 2005). Ya mere, o nwere ike ịbụ na ọ bụghị ihe mgbagwoju anya na dabere na ọgwụ ndị a na-eme n'oge na-adịghị anya, enwere mmụba (psychostimulants) ma ọ bụ belata (opioids)Robinson na Kolb, 1999, 2004; Jedynak et al, 2007). Usoro ihe omimi nke neuroplasticity nke na-achịkwa mmịpịkpụ azụ bụ ebe na-emepụta nchọpụta nke siri ike. Otú ọ dị, ụkpụrụ nke cytoskeleton nke nwere ike ime ka ahụ ma ọ bụ gbanwee ọnụọgụ azụ bụ onye na-eto eto maka usoro nke nwere ike ịmalite mgbanwe na nkwụsị ịkpụ azụ (Rao na Craig, 2000; Lisman, 2003; Blanpied na Ehlers, 2004; Matus, 2005). N'ihi ya, enwere ọganihu na-adịgide adịgide na-eme njem ịgba ọsọ mgbe ị kwụsịrị si na-adịghị ala ala psychostimulant nchịkwa (Ihe niile et al, 2006). Ọganihu nke ịgba ígwè na-eme, ọ dịkarịa ala na akụkụ, site na mbelata Lim kinase, nke nkatọ na-achịkwa F-actin depolymerization, yana spine maturation (Meng et al, 2002; Soosairaja et al, 2005). Na mgbakwunye na nsụgharị na morphology ihe ọzọ na-esi n'ịgbagharị ịgba ígwè na-arịwanye elu ga-agbanwe n 'ịzụ ahịa nke ndị na-edozi n'ime akpụkpọ ahụ postsynaptic (Kasai et al, 2003). Ọ bụ ezie na ọ bụghị isi na-eme ka ịgba ígwè na-arịwanye elu, mgbanwe dị egwu nke dị na trasynaptic tractor trafficking bụ mmụba na-adịgide adịgide n'ime ntinye akpụkpọ anụ nke ndị natara AMPA glutamate (Mangiavacchi na Wolf, 2004; Sun et al, 2005; Boudreau na Wolf, 2005). Otú ọ dị, n'ụzọ dị ịtụnanya, mmụba nke ndị na-anabata AMPA na-enweghị ike imebi ịda mbà n'obi ogologo oge (nke a na - ejikarị jikọtara ndị na - anabata AMPA)Martin et al, 2006). Ọ bụ ezie na a chọpụtara na nchọpụta a n'oge na-adịbeghị anya n'ọmụmụ ihe nke na-egosi na mgbe ha kwụsịrị site na cocaine enwere ọganihu dị elu na AMPA dị ugbu a na mkpụrụ ndụ ntinye mkpụrụ ndụ (Kourrich et al, 2007). N'izugbe, usoro ọgwụgwọ nke electrophysiological nke ịṅụ ọgwụ ọjọọ na ụbụrụ spiny na-eme ka ọ dị ugbu a bụ mpaghara nke mgbagwoju anya na akwụkwọ (Kalivas na Hu, 2006).

N'ụzọ na-akpali mmasị, ndị nabatara BDNF na-akpali akpali na-akwalite ugbo omeebe ma na-eme ka ịdị ọkụ na -Bramham na Messaoudi, 2005), na-egosi na ịrị elu nke BDNF na-aga n'ihu na mbudata nwere ike inye aka kpọmkwem na mgbanwe ndị na-adịgide adịgide na nnyefe nnyefe. N'okwu doro anya nke megidere echiche a, ndị na-anabata BDNF ndị nabatara na accumbens na-akwalite ịchọrọ cocaine (Graham et al, 2007), otu mmetụta na-eme ka ọ ghara imebi ịgba ígwè na NA (Ihe niile et al, 2006). Otú ọ dị, nchọpụta e mere n'oge na-adịbeghị anya gosiri na ntọhapụ nke BDNF n'ime ihe ndị na-akpata ọrịa mgbe gọọmentị ahụ gasịrị na PFC gbochiri ma ịṅụ ọgwụ na-achọpụta cocaine na ịhapụ glutamate nke metụtara cocaine-ịchọ (na-Berglind et al, 2007). A kwadoro na BDNF na-etinye n'ime PFC na-ebugharị ma na-abanye na NA iji mepụta àgwà a (Osisi et al, 1997). N'ihi ya, nkwụsịtụ nke BDNF site n'aka ndị mbụ na-agafe agafe na NA nwere ike ịpụta mmetụta dị iche karịa microinjecting quantities pharmacological.

Ọ bụ ezie na neuroplasticity na-adịgide adịgide na NA na striatum nwere ike igosi hypofrontality nke a na-ahụ na ọgwụ ndị na-adịghị mma, a na-ewere ya na nkwụsị na-adịgide adịgide na-eme na PFC. N'ezie, ugboro ugboro psychostimulant ochichi na-eme ka dendritic spine density na prefrontal pyramidal sel (Robinson na Kolb, 2004). N'adịghị ka mkpụrụ ndụ spiny na ndị na-ebute ebe a na-ejikọta njupụta nke nkedo na ihe na-emeghị ka ọkpụkpụ na -Zhang et al, 1998), mkpụrụ ndụ pyramidal prefrontal dị ka ọ ga - adị mfe ịmalite (Dong et al, 2005). Nke a dabara na mmụba dị ukwuu nke glutamate na-esite na synaptically tọhapụrụ NA NA n'oge a na-achọ ọgwụ, ọ pụkwara, n'otu akụkụ, na-emetụta ya na cellular neuroadaptations dị ka ịbelata akara site na Gi-nke nwere ọnụ ọgụgụ ndị nabatara n'ihi AGS3 dị elu (Kalivas et al, 2005). N'ihi nke a, ebe D2 na-agbanwe mgbanwe mgbasa ozi na-emepụta ihe na-egosi na ọ na-ewepụ ụbụrụ na-adịghị ala ala, ọ na-eme ka mmetụta nke ịrụ ọrụ Gs-tinyere ndị nabatara D1 na -Nogueira et al, 2006). Nke a nwere ike itinye aka na ụba na-arịwanye elu na ọnwụ nke ụbụrụ na-agbapụta na kọlụm mbụ na-eme mgbe cocoine na-adịghị ala ala (Trantham et al, 2002), dị ka ihe ntanye ihe ntanye nke D1 na-akwalite itinye ntinye aka AMPA n'ime akpụkpọ ahụ (Sun et al, 2005). Eziokwu ahụ bụ na onye na-anabata ihe ntanye D1 na PFC chọrọ maka ịmaliteghachi ịchọrọ ọgwụ na-adabere na nke a (Capriles et al, 2003; Sun na Rebec, 2005).

Nchịkọta nke Neuroplasticity nke na-egosi mmezu nke nwube iwu na ịgba aghara

Dị ka egosiri na Nyocha 4c, ụdị neuroplasticity nke na-atachi obi n'oge abstinence na-enye ihe na-adịghị na-adịgide adịgide na-adịgide adịgide vulnerability ka ịlọghachi na riri ahụ. Nnyocha dịgasị iche iche na-akwado ịba ụba nke mbu na-ebute na mbu dịka onye mgbasa ozi siri ike nke ịchọ ọgwụ. N'otu aka ahụ, mgbanwe ndị a gbanwere na postlịptic glutamate signaling, gụnyere mgbanwe nke morphological na ụdọ anọ nwere ike inye aka na mgbanwe. Agbara plasticity na-emetụta ma hypofrontality dị n'oge usoro isi na nzaghachi siri ike nke PFC na ntinye na NA n'oge ịṅụ ọgwụ ọjọọ ma ọ bụ ọchịchọ ọgwụ ọjọọ amalitela ịkwalite elu na, dịka edepụtara n'okpuru ebe a, ọ bụ ebe ịmepụta ihe ọhụrụ maka ịmepụta pharmacotherapies maka ịgwọ ọrịa ịṅụ ọgwụ ọjọọ.

NTỤKWỌ NDỊ ỌZỌ NA-ECHIOKWU NDỊ NA-ECHICHE

Ka anyị na-amụba nghọta anyị banyere usoro sekit na usoro cellular site na iji ọgwụ ọjọọ eme ihe ugboro ugboro na-eme ka ọnọdụ ahụ ghara ịlọghachite, ọganihu ọhụrụ ọgwụ nwere ike ịpụta. Uzo ogwugwu a na-eme ka ndi ozo di iche iche di iche iche na-eme ka ndi mmadu nweta ogwu di iche iche.

Na-agbanwe Mgbanwe nke Iwu

N'iji ọgwụ na-eme ihe iji kwado ikike nke ndị ahụ riri ahụ iji tinyekwuo nkwupụta, usoro mkpebi n'ime nlọghachi dị oké mkpa iji belata nlọghachi ike. Dị ka e depụtara n'elu, mgbanwe ịghaghachị ịghọ àgwà dabere na kọntaktị ncheta na-amaghị ihe na-agụnye nkwụsị nke iwu nchịkwa. Site n'iji ọgwụ ọjọọ eme ihe a na-egosipụta nke a site na mbelata uche na-arụ ọrụ ndị metụtara nchebara echiche, impulsivity na ike ịgbanwe omume dabere na ozi ọhụrụ. Dabere na nchọpụta ndị a, ịmepụta ma ọ bụ igbochi neuroplasticity na-emepụta na PFC iji dozie usoro ịkpa ndị dị egwu ga-adị ka ihe bara uru. Dika edewara n'elu, mgbanwe ndi ogwu di iche iche na-emetuta ihe ndi ozo na-akpata n 'ugwo oria site na nzapu dopamine, wee bulie ya elu iji mee ka ndi mmadu ghara icho ogwu. Ya mere, ọgwụ ndị na-agbanwe nhazi dopamine, nnyefe glutamate ma ọ bụ nnyefe GABA bụ ndị nwere ohere. Ọzọkwa, ihe gbasara GABA site na NA na-edochi ya na ọtụtụ neuropeptides (McGinty, 2007), na peptides ndị a, yana ndị ọzọ nọ na corticolimibic bụkwa ndị na-aga maka mmepe ọgwụ.

Dopaminergics

Ntinye nke Dopamine na-enwe mgbanwe dị iche iche dabere na subtype natara. Ya mere, enwere mbelata na akara ngosi ntinye aka D2 (Volkow et al, 2004), nke nwere ike ịbawanye na D1 (Kalivas et al, 2005), na ọkwa dị elu na ndị nabatara D3 n'ihi nhụsieke na-abawanye na BDNF (Neisewander et al, 2004). Nke a na-eme ka o sie ike ịkọ ụzọ kachasị mma maka ịmepụta dopamine. Otú ọ dị, e nwere ezigbo nkwado data na-akwado iji D3 eme ihe iji gbochie ịṅụ ọgwụ ọjọọ (Xi et al, 2006).

Glutamatergics

Dabere na mmechi ahụ nke edepụtara n'elu, igbochi nkwụsị nke glutamate synaptic nke jikọtara ọgwụ na-achọ ga-abụ ụzọ kachasị mma iji belata mkpali ịlaghachi azụ. Otú ọ dị, ọ gaghị ekwe omume iji ndị na-eme ka ndị na-anabata ionotropic glutamate zuru ezu na-emetụta ya n'ihi mmetụta ndị na-adịghị anakwere. N'ihi ya, usoro dị iche iche nke ọgwụ na-apụta maka ịmepụta kama igbochi nnyefe glutamate. Ụfọdụ n'ime ogige ndị a abanyeworị n'ime ule na-ahụ anya ma gosi ịdị mma dị ala. Dịka ọmụmaatụ, acamprosate na topiramate nwere ihe na-adịghị ike dị ka onye na-anabata onye ọrụ AMPA (Myrick na Anton, 2004; Cubells, 2006). A kọwaara Topiramate iji belata nlọghachi na ịṅụ ọgwụ cocaine (Kampman et al, 2004). Ọzọkwa, modafinil na N-acetylcysteine ​​na-eme ka iwelie extracellular glutamate ma si otú ahụ na-akpali mgbochi mGluR nke mgbochi nke synaptic glutamate ntọhapụ egosiputa nrụpụta ọrụ na nlọghachi azụ cocaine ma ọ bụ na-achọsi ike,Azụ et al, 2005; LaRowe et al, 2007). Atọ ndị nwere onwe ha atọ akọwawo (Azụmahịa, 2004; Malcolm et al, 2006; Hart et al, 2007) na modafinil na-ebelata nnukwu cocaine site na ịba ụba glutamate na-arụ ọrụ na-arụ ọrụ mGluR dika akọwapụtara n'elu. Ọzọkwa, n'usoro ihe eji eme ihe, a na-egosipụta mGluR2 / 3 agonists iji gbochie ịṅụ ọgwụ ọjọọ (Baptista et al, 2004; Peters na Kalivas, 2006).

GABAergics

Ụdị cocaine na heroin na-egosi na mbelata GABA n'ime VP site n'aka NA afferents na-achọ ọgwụ (Caille na Parsons, 2004; Tang et al, 2005). N'ịkwado mkpa nke mmegharị a, ọgwụ ndị na-akwalite nnyefe GABA egosiputa nkwa na nkenke na nkenke ọmụmụ, vigabatrin (onye na-emechi GABA transferase), gabapentin (usoro doro anya), na baclofen (GABAb agonist). Onye na-agụ ya na-atụle nyocha ndị na-adịbeghị anya banyere iji GABAergics na-agwọ ọgwụ ọjọọ (O'Brien, 2005; Vocci na Ling, 2005).

Peptidergics

A na - edozi ọtụtụ neuropeptides na GABA site na NA, gụnyere neurotensin, ihe P, dynorphin, na CART (McGinty, 2007). Ọ bụ ezie na anyị maara banyere otú ndị a peptides si enye aka ma ọ bụ ịhazi nduzi ọgwụ ndị na-agba mbọ site na ndị na-ebute na pallidum projection bụ dịtụ ogbenye, e gosipụtara na igbochi ndị na-anabata enkephalin na VP na-egbochi ịchọ cocaine na ụdị anụmanụ (Tang et al, 2005), mmetụta nwere ike itinye aka na naltrexone nke na-eri ahụ nke ethanol (Vocci na Ling, 2005).

Mkpebi

Ọ bụ ezie na e nweela ọganihu dị mkpa na nghọta anyị banyere neuroplasticity nke na-ebute mmebi nke ahụ riri ahụ na nhụjuanya na-adịgide adịgide ịlọghachite, anyị na-enwe ọganihu n'inwe ike itinye ihe ọmụma ọhụrụ a iji na-emeso ọgwụ ọjọọ. Ọ bụ ezie na anyị nwere ụfọdụ ndị na-ahụ maka ọgwụ na-emepụta ọgwụ na-achịkwa ntanetransite n'etiti eriri dị na sekit gosiri na ọ dị mkpa, ọ na-esiri ike ịchịkwa neuroplasticity nke emepụtara na njigide intracellular nke dị oké njọ maka ịṅụ ahụ. Iji ozi ọhụrụ a na-echere mmepe nke ogige ịhọrọ maka ndị na-edozi a na-eche nche na ụzọ nrịba ama, ma dị mkpa karị, pụtara iji zipu ogige ndị ahụ. Ka o sina dị, ọdịdị nke neuroplasticity e mere ka ọ pụta ìhè na-egosi ụzọ maka usoro ọgwụgwọ n'ọdịnihu nke ga-adị ka nkà na ụzụ na-enyefe ihe.

Notes

AGBA

Dr O'Brien jere ozi dị ka onye ndụmọdụ n'ime afọ atọ gara aga na Alkermes, Cephalon, Forest na McNeil Laboratories. Dr Kalivas enweghị ihe ọ bụla igosipụta.

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