Mukhaadaraadka Daroogada ee loo yaqaan 'Pathology of Neuroplasticity' (2007)

1. ¹Waaxda Dumarka, Jaamacadda Caafimaadka ee South Carolina, Charleston, SC, USA
2. ²Waaxda Maskaxda, Philadelphia VA Medical Center, Jaamacadda Pennsylvania, Philadelphia, PA, USA

Wareysiyada: Dr P Kalivas, Waaxyaha Qalabka Xuurnimada, Jaamacadda Caafimaadka ee South Carolina, 173 Ashley Ave, BSB 410, Charleston, SC 29425, USA. Tel: + 1 843 792 4400; Fax: + 1 843 792 4423; E-mail: [emailka waa la ilaaliyay]

aan la taaban karin

NEUROPLASTICITY AND TIXJIYADA HUBINTA

Dib-u-eegistaan, neuroplasticity waxaa loo adeegsan doonaa laba qaybood: marka hore, isbeddel ku yimaada waxqabadka neuronal ee soconaya saacado illaa todobaadyo ah daroogada daroogada, iyo labaad, isbeddel deggan oo soconaya mudo todobaadyo ah si ay u noqdaan isbedel joogto ah. Xanuunka neuroplasticka wuxuu u dhigmaa isbeddellada lagama maarmaanka u ah horumarinta dabeecad cusub, halka neuroplasticka xasillooni ku habboon yahay xogta xasilloon oo laga soo qaado si loo hago fulinta dhaqanka bartay. Isticmaalka walbahaarka, marxaladahaas ayaa guud ahaan lagu sharraxayaa sida horumarinta maandooriye (tusaale ahaan, barashada inay noqoto mid liidato), iyo xaalad xasillooni daro oo sare u kac ah oo soo noqnoqonaysa ka dib joojinta qaadashada daroogada. Horumarinta maandooriyaha waxaa sida caadiga ah lagu gaarsiiyaa isticmaalka bulshada ee soo noqnoqoshada daroogada, waxayna ku lug leedahay isbeddel waqti gaaban oo nafsami ah oo nafsadeed iyo cilmi-nafsi maskaxeed oo ku saleysan falanqaynta farmashiga ee daroogada lafteeda (Nestler, 2005). In Jaantus 1a, marxaladdan waxaa loo yaqaanaa isticmaalka bulshada. Marxaladda labaad waxaa lagu sameeyaa caymis soo noqnoqda oo soo noqnoqda oo ku salaysan isbeddelka isbeddelka physiology ee maskaxda maskaxda oo xukuma garashada iyo dareenka ee ka jawaab celinta dareenka deegaanka. Tani waxaa lagu muujiyey Jaantus 1a laba waji oo dib u gurasho ah. Wajiga koowaad ee dib u gurashada waxaa lagu qeexay dib u soo noqoshada nidaamsan, labaadna sidii dib u noqoshada khasabka ah. Dib-u-habeyn la xakameeyey ayaa loola jeedaa habka go'aaminta ee ra'yi-bixinta taas oo qofkasto-doonku si qarsoodi ah u go'aansado in uu ku laabto. Tusaale ahaan, shakhsiga ayaa laga yaabaa inuu sameeyo ikhtiyaarka u dhexeeya ka caawinta ilmahooda shaqada guriga ama cabitaanka galaas khamri ah. Marxaladdan, addict-ka ayaa badanaa doortay doorasho bulsho oo ku habboon. Dib u laabashada qasabka ah, maandooriyuhu maaha inuu samaysto doorasho miyir leh. Tusaale ahaan, inkasta oo ka caawinta ilmahooga shaqada casharrada guriga, waxay noqon kartaa sheyga ajandaha ee fiidkii, soo-jeedinta calaamadaha deegaanka ee kala duwan ama walbahaarka oo shakhsigu uu la xiriiro isticmaalka daroogada ee soo noqnoqday wuxuu kicinayaa daroogada-raadinta, iyo go'aanka miyir-qabka ah marna lama samayn, qofka si toos ah ayuu u soo noqdaa.

Sida iska cad, dib-u-dhac khasab ah waa waji ka sii daran oo, sida aan arki karno, waxaa ku jira bartilmaameedyada neuropathological ee lagu hormarinayo waxqabadyada dawooyinka dawooyinka. Sida lagu muujiyey Jaantuska 1, waxaan soo jeedineynaa dhamaadka dib-u-eegistaan ​​taas oo ku saleysan xanuunka neuropathology ee dib-u-soo-kabashada khasab ah oo ah qaab nulloblastic ah oo xasilan, doorka ugu muhiimsan ee daaweynta cilmi-nafsiga ee daaweynta mukhaadaraadka waa horumarinta mukhaadaraadka kor u qaadaya dib-u-dhac qasab ah. Si kale haddii loo dhigo, farmasiyada daaweynta qiimaha badani waxay noqon doontaa kuwa fududeeya go'aan qaadashada firfircoon, oo u oggolaanaya inay xakameeyaan inay qaataan daroogada. Taa beddelkeeda, ka gudubka dib-u-dhicida loo maro isticmaalka bulshada ama ka-go'naanta waxaa si fiican loogu daaweynayaa daawooyinka faraha iyo hab-dhaqameedyada xoojiya oo taageeraya go'aamada saxda ah (Centonze et al, 2005). Tusaale ahaan, waxqabadyada anshaxeed waxay ka koobnaan kartaa hababka caadiga ah sida tababarka iyo dabeecadda garashada ee garaadka, si loo helo shaqo joogta ah ama dib ula midoobid kuwa la jecel yahay.

Heerarka Saamaynta iyo Darajooyinka Waxbarashada Abaalmarinta ah ee caadiga ah

Jaantus 1b isku dayga in lagu muujiyo fahamkayaga imika ee xusuusta baylahnimada iyo hababka barashada iyada oo la marayo marxaladaha qabatinka (Kelley, 2004; LaLumiere iyo Kalivas, 2006). Sidaa daraadeed, helitaanka xasuusta iyo horumarinta jawaabaha habdhaqanka ee habdhaqanka ah ee dhiirigelinta muhiimka ah waxaa loo yaqaannaa helitaanka iyo u dhigma isticmaalka daroogada bulshada. Miisaaniyadda loo dejiyay dib-u-celinta ayaa ah soo noqoshada xasuusinta caddaynta, taas oo ah, xusuusta laga hadlayo oo loo adeegsado go'aan qaadasho miyir leh. Ugu dambeyntii, dib u noqoshada khasabka ah waxaa loo tixgelin karaa mid la mid ah ciyaalka ama xasuusta habka. Dib u soo celinta xasuusta habka aan la sheegin looma sheegin, waxaanay hagaysaa miyir beelka dabeecadaha la qabsiga. Dabeecadahaan si fiican ayaa loo barto oo ay si wax ku ool ah u socdaan iyada oo aan go'aan laga gaarin (tusaale ahaan, baaskiil, ama furitaanka albaabka qaboojiyaha marka ay gaajeysan yihiin).

Waxaa jiray horumar ballaaran oo tobankii sano ee la soo dhaafay ku yimid fahamkayaga xuddunta maskaxda iyo neurotransmitters doorka muhiimka ah ee xusuusta dhiirigelinta ah ee la helay, iyo dabeecadaha la bartay ee la dilay. Arin aad uwanaagsan, aqoon badan ayaa ka soo baxday geeddi-socodka helitaanka falanqaynta ee cilmi-baarayaasha oo baranaya habab waxbarasho oo dhiirigelin leh iyo kuwa wax ka baranaya takooridda daroogada sida baaritaanka barashada caadiga ah. Jaantus 1b waxay muujinaysaa sida xeeladaha muhiimka ah ee wareega maskaxda iyo nihotransmitters ee ku haboon marxaladaha ku-takoorka. Sidaas daraadeed, barashada in lagu daro isticmaalka mukhaadaraadka mukhaadaraadka ayaa si xoog leh ugu lug leh unugyada dopamine ee ku yaala ventral tegmental (VTA) oo dopamine sii deynaya kiliyaha hore (PFC), amygdala, iyo nucleus accumens (NA) (Berridge iyo Robinson, 1998; Kelley, 2004; Schultz, 2004; Xigmad, 2004; Jones iyo Bonci, 2005). Hal canshuur oo macquul ah oo lagu taageerayo qaababka xayawaanka ayaa ah in sida daroogada loo raadsado ay noqoto mid si fiican loo barto, oo ku tiirsan dhaqanka qiyaasaha glutamaterka ee PFC ilaa NA soo baxa (Pierce iyo Kalivas, 1997; Cardinal iyo Everitt, 2004; Wolf et al, 2004). Sidaa daraadeed, dib-u-celinta nidaamsan waxay si xooggan ugu xiran tahay dib u soo celinta xusuusta daroogada la xidhiidha iyo is-dhexgalinta xusuus-qoraalkaas iyada oo loo marayo saadaalinta gluteamaterka ee PFC-ga NA. In kastoo glutamate ay sii wadaan inay door weyn ku yeeshaan dib-u-kicinta khasabka ah ee noocan ah, wareegga glutamatergic-ka ee ka soo wareega wareega hore ee maamulka ee wareega wareegga ah ee ku lug leh wareegtada cortico-striott-thalamic model, iyo xusuusta hab-dhaqameed ee xoojinta ka-qaybgalka dabeecadaha wanaagsan (Barnes et al, 2005; Everitt iyo Robbins, 2005).

Inta ka hartay dib-u-eegiddani waxay ku lug leedahay qoto dheer oo ka soo baxa neuroplasticnimada oo ka hooseysa marxaladaha xirribaggubka, iyo is-dhexgalinta neuroplastic-ka taas oo loo marayo rajooyin cusub oo ku saabsan horumarinta daroogada cusub ee loogu talagalay dadka ka soo jeeda dadka ka soo jeeda qallafsan si dib-u-habeyn loo nidaamiyo.

WAXYAABAHA LAGA HELI KARTAA WAXYAABAHA LAGA HELO DAWEYN

Sida ku qoran Jaantuska 1, isticmaalka daroogooyinka soo noqnoqda (isticmaalka daroogada bulshada) waxay ku lug leedahay soo noqnoqashada sii dopamin ee unugyada VTA-ga ee PFC, oo ah xeel dheer (oo ay ku jiraan NA), iyo amygdala. Qaabkan waxaa lagu muujiyey gudaha Jaantus 2a. Marka la eego dareenka nafleyda ku habboon ee nafaqada leh, dhammaan daroogooyinku waxay kordhiyaan xayawaanka dopamine gudahood wareeggaas, inkastoo ay jiraan habab kala duwan oo farsamo (Jay, 2003; Kelley, 2004; Nestler, 2005). Xiriirkani wuxuu udhaxeeyaa kor u qaadista dopamine iyo dabeecadaha barashada si loo helo abaal-marin waxay keentay in la fahmo in dopamine sii daayo ay tahay dhacdo muhiim ah oo lagu fududeynayo barashada. Sidaa daraadeed, daraasado badan ayaa muujinaya in xoojinta dopamine in la yareeyo dhiirigelinta iyo barashada, halka kor u qaadista dopamine caadi ahaan kor u qaadaan dabeecadaha la bartay. Dopamine sii deynta ayaa la siidaayay si ay u muujiso dhacdo leh salience, oo abuuraya dareen gudaha ah in tani ay tahay dhacdo muhiim ah oo u baahan in la horumariyo jawaab celin habdhaqaneed (Berridge iyo Robinson, 1998). Waxyaalaha muhiimka ah ee u dhexeeya waxaa ku jira dopamine oo la sii daayo daawooyinka khatarta ah vs dhiirigelinta dareenka deegaanka, iyo kala soociddaan waxaa loo maleynayaa in ay muhiim u tahay horumarinta daroogada loo xakameynayo iyo kuwa khasaaraya.

Jaantus 2b waxay muujineysaa laba kala-gaddisan oo u dhexeeya dopamine sii-deynta kobcinta dhiirigelinta nafleyda vs ka dib markii lagu soo bandhigo daroogo xariif ah. Marka hore, sii dopamine by daroogada addictive waa xajmiga weyn iyo muddada ka badan la gaari karaa iyada oo loo marayo hababka physiological. Si fudud ayaa loo dhigaa, daawada dawooyinka ee daroogada ayaa xawilaadda dopamine ka baxsan xuduudaha jir ahaaneed iyada oo ka gudubtay hababka caadiga ah ee guryaha oo lagu xakameynayo dopamine sii deynta. Tusaale ahaan, amphetamine-like psychostimulants ayaa hor istaagaya joojinta dopamine oo ka soo baxa synapses, xaaladaha qaarkoodna waxay kor u qaadaan daaweynta dopamine presynaptic (Seiden et al, 1993), halka daroogooyinka kale sida nikotiinka ama opioids ay wax ka beddelaan nidaam celinta jawaabta ee unugyada dopamine, taas oo keeneysa in kororka firfircoonida unugyada. Sidaa daraadeed, nicotin waxay kor u qaadeysaa gudbinta xanuunka glutamate ee VTA, halka opioids ay hoos u dhigto xayiraadda GABA-da ee dopamine neurons (Nader iyo van der Kooy, 1997; Laviolette iyo van der Kooy, 2004; Pierce iyo Kumaresan, 2006). Farqiga labaad ee ugu weyn ee lagu muujiyay Jaantus 2b inta u dhaxaysa sii-deynka dopamine ee daroogada iyo taas oo soo saaro dareemaha bayoolojiga, waa in dulqaadku uu kobciyo siideynta dopamine by dareenka noolaha, halka daroogada daawada loo sii daayo dopamine mar kasta daawada la qaato. Isticmaalayaasha joogtada ah, kordhinta qiyaasta ayaa loo baahan yahay sababtoo ah dulqaad, laakiin leh qiyaas ku filan, kor u kaca dopamiin waxay u egtahay mid si wax ku ool ah u dhacda. Marka laga reebo tani waxaa ka mid ah barafka oo leh astaamaha amphetamine-sida psychostimulants, taas oo keeni karta dhicin waqti gaaban oo ah dadka isticmaala dopamine iyo dabacsanaanta dabaysha kuwaas oo soo sheegey maqnaansho aad u daran ama dulqaadka ah saamaynta firfircoon ee daroogada iyada oo loo marayo habab aan weli la aqoon (Martinez et al, 2007). Sidaa darteed, abaalmarinta bayoolojiga, marka qofku barto habdhaqanka ugu fiican si uu u helo abaalmarin, dopamine sii daayo si loo fududeeyo barashada dheeraadka ah lagama maarmaan mana dhacdo (Deutch iyo Roth, 1990; Schultz, 2004). Si kastaba ha ahaatee, waxaa muhiim ah in la ogaado in dopamine uu sii wadi doono inuu calaamad u ahaado imaatinka abaalmarinta dareenka xaaladdiisa (Schultz, 1998). Tusaale ahaan, hadaba keenitaanka abaalmarinta cuntada ee ka jawaab celinta xaashida xaaladaha dabiiciga ah waxaa laga yaabaa inaanay kicin xayiraadda dopamine ee xayawaan loo tababaray, muuqaalka cue ee horey loogu soo bandhigay raashinka cunnadu wuxuu kordhin doonaa xakameynta unugyada dopamine, taasoo u maleynaysa inuu diyaarinayo xayawaanka si uu u bilaabo cuntada la qabsashada - jawaab celinta. Sidaa awgeed, dopamine waxay u adeegtaa laba hawl, (1) si loo fududeeyo barashada bilowga ah ee wax ku ool ah ee wax ka qabashada dareenka muhiimka ah, iyo (2) si loogu soo gudbiyo xogta loo baahan yahay si loo fuliyo jawaab celinta dabeecada ah marka xaaladaha deegaanka ay saadaaliyaan in cuntada dhow. Taa bedelkeeda, maamul kasta oo ka mid ah abaalmarinta daroogada ah ee la qabatimay waxay la xiriirtaa dopamine weyn oo la filayo in lagu hormariyo barashada cusub (sida ururo cusub oo u dhexeeya daroogada iyo deegaanka) ama xoojinta barashada hore, iyo sidoo kale in lagu cambaareeyo fulinta dabeecada daroogada raadinta (ie dib u noqoshada). Moodooyinka xayawaanka, tilmaamayaashu waxay sidoo kale kordhin karaan jawaabta dareen-kiciyeyaasha sidaas oo ay soo saaraan jawaab-celin wax-qabad ah oo ku saabsan qiyaasta tallaal-bixiyaha ah. Sidan oo kale, isticmaalka soo noqnoqoshada daawooyinka la qabatimay waxay kor u qaadaa ururada sii kordhaya ee u dhaxeeya munaasabadaha nolosha iyo daroogada, halka dareenka nafleyda ee muhiimka ah uusan samayn. Tani waxay ku xiran tahay sababta daroogada loo isticmaalo isticmaalka daroogada sababta keenta dabeecadaha daroogada raadinaya si ay uga gudubaan dhammaan dhinacyada nolosha nolol maalmeedka qofka oo noqda mid ku tiirsan.

Sida kor ku xusan, daawooyinka kala duwan ee xadgudubka sii dopamine iyada oo loo marayo hababka kala duwan ee molecular. Mid ka mid ah ficillada ethanol ayaa ah mid u ololeynaya nidaamka dhammeystiran ee opioid sidaa daraadeed haddii haddii qolalka opiate-ka ay xannibaan antagonist sida naltrexone, kororka dopamine-ka ee khamrigu sababo ma dhicin oo abaalmarintana waa la xiraa (Gonzales iyo Weiss, 1998). Sidaa daraadeed, muujinta habdhaqanka ee baqshiinka dadka ku takrifalka ah ayaa laga yaabaa inay ku kala duwan yihiin sida daroogada. Xanuunada heroin-ka ah, tusaale ahaan, isticmaalka daroogada ee soo noqnoqota waxay soo saartaa dulqaadka calaamadeysan oo leh calaamado xaddidan oo soo saaraya jawaab celin soo-horjeeda ama ka-soo-jiidasho leh (O'Brien, 1975; O’Brien et al, 1977). Calaamadaha daroogada ee daroogada kookayntu waxay soo saaraan kookeynta cocaine-ka iyo dhaqdhaqaaqa limbic (Dhallaanka et al, 1999) iyadoo lala xiriirinayo dopamin dheellitiran (Volkow et al, 2006). Guud ahaan, takoorka aadanaha, dulqaadka ayaa ah neurootiga inta badan lagu arkay xitaa daroogada cocaine (O’Brien et al, 2006). Tani waxay keenaysaa in la kordhiyo qiyaasta daawooyinka iskiis loo maamulo si loo gaaro saameynta daroogada asal ahaan laga soo helay.

Daaweynta Neuroplastic-ka ee Dopamine-ku-keena

D1 iyo delta-FosB xawaareynta calaamadda

Dopamine-ka sii deyntiisa ayaa leh xayawaan muhiim ah ama daroogo xoojin ah ayaa soo saara isbeddel ku yimaada sida qanjidhada loo dhexgeliyo neurotransmission. Dhibaatooyinka firfircoonida dopamine ee dib-u-dhaqaajinta ayaa ah mid adag oo kala-duwanaansho u dhexeeya dhaqdhaqaaqa D1-sida vs D2-like reseptors waxay ku xiran tahay joogitaanka xeryaha hore iyo postinaptic ee gudaha gudaha wareega nucleus. Waxaa jira tiro dib u eegis heer sare ah oo tilmaamaya xaaladda hadda jirta ee aqoonta ku saabsan dopamine signaling sida ay ku lug leedahay mukhaadaraadka iyo waxbarashada dhiirrigelinta ah (Berke iyo Hyman, 2000; Nicola et al, 2000; El-Ghundi, 2007). Ujeeddooyinkeenna, Jaantuska 3 waxay muujinaysaa dhacdooyinka muhiimka ah ee tooska ah ee D1 dib u habeyn lagu sameynaayo oo loo maleynayo inay muhiim u tahay horumarinta isbeddelka joogtada ah ee jirdhiska maskaxda oo hoos yimaada dejinta dabeecadaha la qabadsiiyo ee dhacdooyinka dhiirrigelinta ku haboon, iyo sidoo kale dabeecadaha daroogada raadraacaya. Muhiimad ahaan, qashinkaas tilmaamaya waxa ku jira isbeddelada kudhaca gawrida iyo dib-u-hagaajinta cusbooneysiinta kuwaas oo loo maleynayo in ay hoosta ka soo wareegayaan isticmaalka bulshada si dib-u-habeyn loogu sameeyo iyo dib-u-dhicin. Sidaa daraadeed, kicinta xayawaanka D1 ee ku yaala striatum iyo kortex waxay kordhinayaan cAMP, KAMP-kinase protein kinase (PKA), iyo cAMP jawaab celinta istiraatiijiga ah (CREB) kaas oo kor u qaadaya qoraalka gen ee badan oo ku lug leh qabatinka, sida cfos, deltaFosB, Homer, iyo preprodynorphin (Hurd iyo Herkenham, 1993; Nestler et al, 2001; McClung iyo Nestler, 2003; Benavides iyo Bibb, 2004). Muhiimadda, kor u kaca CREB ee NA iyo, in yar, VTA waxa lala xiriiriyay xoojinta daroogada oo hoos u dhacday (Carlezon et al, 1998; Nestler, 2005). Inkasta oo dhammaan maandooriyeyaasha maandooriyeyaasha ahi aysan u muuqan inay kor u qaadayaan CREB calaamadahaPandey et al, 2004), xad-dhaafka ah ee CREB ee ku-soo-galayaasha ayaa hor istaagaya saamaynta abaal-marinnada nafsiga ah ee nafsiyaadka, miyuusiyaadka, iyo abaalmarinta nafleyda, halka sare-u-qaadista iskudhufka 'CREB mutant' ay kor u qaadaan abaalmarinta daroogada (Barrot et al, 2002; Lu et al, 2003; McClung iyo Nestler, 2003). Waxa xiiso leh, daraasadihii qaarkood waxay muujinayaan in CREB ay lagama maarmaan u tahay saameynta abaalmarinta daawooyinka xoojinta iyo xoojinta nafleyda (Jin et al, 2005; Walters et al, 2005; Choi et al, 2006), oo muujinaysa suurtagalnimada in xeerka degdega ah ee CREB loo baahan yahay dabeecadaha dhiirigeliya, kor u qaadista soo noqnoqoshada ee CREB waxay u keentaa dulqaad si loo xoojiyo saameynta sii xoojinta dareenka. Qaybo unugyada CREB-ga ah, sida preprodynorphin, NAC-1, iyo Homer, waxay shaki ku jirtaa inay saameyn ku yeelaneyso CREB si loo yareeyo qiimaha daroogada. Tusaale ahaan, dynorphin oo korodhey waxqabadka unugyada dopamine iyo dopamine release presynaptic (Carlezon et al, 1998; Macaaneeye et al, 2000; Hyman et al, 2006), iyo fayruska fayruuska ee NAC-1 ama Homer1c ee calaamaduhu waxay horjoogsadaan horumarinta dabeecadaha dareemayaasha ah ee dareemayaasha ah ee kookiinka soo noqnoqda (Mackler et al, 2000; Szumlinski et al, 2006). Muhiimad ahaan, laba ka mid ah borotiinnada, preprodynorphin iyo NAC-1 waxay muujiyaan kor u qaadista joogtada ah ee ka-go'naanta, taas oo muujinaysa in muddada dheer ee bixinta lacag-bixinta dheeraadka ah ee abaalmarinta daroogada (Hurd iyo Herkenham, 1993; Cha et al, 1997). Nasiib darro, sida lagu falanqeynayo faahfaahin hoose, dulsaarista abaal-marinta daroogada ayaa sidoo kale sii wadi karta abaalmarinta nafleyda.

Xubnaha CREB-ku-habboon, kororka xakamaynta gawaarida, DeltaFosB, ayaa muujiyay gaar ahaan xiiso (Nestler et al, 2001). Korodhka jaangooyooyinka badan ee transcriptal iyo gen cajiinka hore ee ayadoo la adeegsanaayo daroogooyinka la qabatimay ama dareenka dhiirigelinta nafleyda, sida cfos, Arc, Homer1a, iyo nacayb, ka dib markii soo noqnoqodka soo noqnoqda. Taas bedelkeeda, deltaFosB waxay ku ururtaa beeraha dopamine-terminal oo ku yaal kortex iyo striatum (Nestler et al, 2001; McClung iyo Nestler, 2003). Isku soo uruurintani waxay ku dhacdaa jawaab celinta daba-galka dhammaan daawooyinka la-tacaalidda ilaa imtixaanka, iyo sidoo kale iyada oo laga jawaabayo dareen-celiyeyaasha soo noqnoqda ee soo noqnoqda. Sidaa darteed, isku-darka ah ee DeltaFosB waxay u badan tahay in ay muhiim u tahay barashada iyo horumarinta dabeecadaha dhiirigeliya guud ahaan. Marka laga hadlayo daawooyinka la qabatimay, daawada faytoomiinka ama khalkhalka hidde-wadeeyntu waxay hor istaagtaa horumarinta noocyo gaar ah oo ah mabnuuc ku xirnaansho-takoorka dabeecadda, sida dhaqdhaqaaqa dhaqdhaqaaqa jirka (Nestler et al, 2001; McClung iyo Nestler, 2003). Qeyb ka mid ah jaangooyooyinka ay soo saareen CREB, qaar ka mid ah jinsiyada si toos ah u maamulaan deltaFosB waxay noqon kartaa magdhow waxayna u adeegtaa xaddidaadda xoojinta daroogada, iyo laga yaabo inay daawo u raadsato (Nestler, 2005). Sidaas daraadeed, induction of Cdk5 phsophorylates dopamin-regulated phosphatase DARPP-32, taas oo ka hortageysa fosforyelka iyo dhaqdhaqaaqa by PKA (Benavides iyo Bibb, 2004). Si kastaba ha ahaatee, soo saarista hiddo-galeedyo kale oo laga helo deltaFosB waxay u badan tahay inay kor u qaaddo abaal-marinta daroogada iyo inta badan daraasaduhu waxay muujinayaan in xad-dhaafka ah ee deltaFosB ay kordhiso abaal-marinta daroogada (Kelz et al, 1999; Colby et al, 2003; Zachariou et al, 2006). Tusaalooyinka nidaamka hidda-gunta deltaFosB ee kor u qaadaya abaal-marinta daroogada waxaa ka mid ah soo-saarista GluR2 ee qolofta hantida (Todtekopf et al, 2006), iyo xakamaynta muujinta dynorphin (Zachariou et al, 2006). Waxaa muhiim ah, soo saarista deltaFosB iyo alaabada hiddaha ay u egtahay inay u muuqato in ay noqoto mid aad u kacsan oo caadi ah inta lagu gudajirayo. Sidaa darteed, inkasta oo ay muhiim tahay helitaanka dabeecadaha daroogada raadinaya, deltaFosB lafteeda maaha tusaale tusaale ah neuroplastic daroogada oo si deggan oo toos ah u dhexdhexaadinta fulinta xukunka ama dib-u-habaynta. Xaqiiqdii, waa dabeecadda ku-meel-gaadhka ah ee saldhigga deltaFosB taasoo ka dhigaysa musharaxa ugu habboon ee borotiinka dhexdhexaadinta ka-beddelashada isticmaalka bulshada si dib loogu isticmaalo isticmaalka daroogada (Nestler et al, 2001). Sidaa awgeed, halka deltaFosB ay soo saartay hindhistaha hiddesidaha laftiisa waa mid ku-meel-gaadh ah, neuroplasticity oo lagu xakameynayo hidde-yadaasi waxay noqon kartaa mid aad u xasilloon inta lagu gudajirayo. Tusaale ahaan, kororka joogtada ah ee cufnaanta lafdhabarta dendritic ayaa lagu soo waramey in uu ku dhaco unugyada laf-dhabarka inta lagu guda jiro isticmaalka daaweynta nafsiga ah ee joogtada ah (Robinson iyo Kolb, 2004), iyo kororintani waxay dhexdhexaadineysaa qayb ka mid ah kicinta deltaFosB ee Cdk5 (Norrholm et al, 2003).

Soo koobid, kicinta D1, CREB, iyo barta deltaFosB waxay si cad u ahaataa mid loo baahdo in lagu wado dareemaha neuroplastic-ka ee ka hooseeya labadaba barashada dhiirigelinta noolaha iyo horumarinta dabeecadaha daroogada raadinaya (Nestler, 2001; Hyman et al, 2006). Si kastaba ha ahaatee, doorka loogu talagalay ku-meel-gaadhka daroogada ee ku-meel-gaadhka ah ee ku-meel-gaadhka ah ee fulinta daroogada-raadinta ama jilicsanaanta soo noqoshada waa mid adag. Tusaale ahaan, muddada gaaban iyo joogto ah ee neuroplasticity ee ku saleysneyd dhaqdhaqaaqa CREB waxaa badanaa la arkaa inay u adeegto shaqeyn magdhow si loo yareeyo dopamine ama glutamate ku faafa calaamadaha, halkaasoo kor u kordhay deltaFosB waxay xakameysaa muujinta hiddaha ee habka labadaba (Cdk5 ) iyo taageeridda abaalmarinta daroogada (korodhka GluR2, dhicin dynorphin). Iskudarkan guud ahaan wuxuu hoos u dhigi doonaa qiimaha qiyamka ee dhiirigelinta nafleyda, iyo tani waxay si aan toos ahayn uga qayb qaadan kartaa jilicsanaanta joogtada ah si dib loogu soo celiyo daroogada. Sidaa daraadeed, adigoo u shaqeynaya qaab magdhow ah oo loola jeedo dhammaan abaalmarinnada, saamaynta unugyada jirka ee durbadiiba ee awoodda ku-meel-gaadhka ah ee D1-CREB signaling (tusaale dynorphin, NAC1, iyo Homer1c) waxay kor u qaadaan daroogada raadinta iyagoo ku helaya abaalmarinta nafleyda.

Nidaamka Xanuunka-Bariiska ee Xanuunka-Baaxadda leh ee Xaddidaadda Sinjiga ee Ku-Meel-Gaarka

Isbedelka dopamine-ku-tiirsan ee isku dhejinta borotiinka ee u muuqata mid gaar ah oo muhiim u ah aasaasidda fiyotoolojiga iyo sidoo kale daroogada loo yaqaan 'neuroplasticity' ayaa ah kor u kicinta calaamadaha neurotrophic ee maskaxda (BDNF). BDNF waxay ku jirtaa fasalka dabeecadaha degdega ah ee dhakhso ah, oo ay ku jiraan Arc, c-fos, iyo zif / 268 (Dunais iyo McGinty, 1994; Moratalla et al, 1996). Si kastaba ha noqotee, BDNF iyo Arc ayaa u muuqda mid u gaar ah sababta oo ah mRNA si xoog leh ayey u soo jiidatay oo ay u qaadeen dendrites ayadoo loo marayo dhaqdhaqaaqa gacanta (Steward iyo Worley, 2001). Danta gaar ahaaneed, iyo muuqata muuqata ka soo jeeda geedka jaangooyooyinka ay qabaan deltaFosB, iyo sidoo kale gen genus-ku xiran waxqabadyada nafsiga ah, isbeddelada joogtada ah ee BDNF waxay ku urursan yihiin mudooyin sii kordhaya ah (Grimm et al, 2003; Lu et al, 2004a; Filip et al, 2006). Sidoo kale, kicinta duubayaasha BDNF ee amygdala, NA, ama VTA waxay dhiirrigelisaa (Horger et al, 1999; Lu et al, 2004b; Graham et al, 2007; Pu et al, 2006), halka xakamaynta micnaha BDNF ee PFC ay joojinayso daroogada-raadinta (Berglind et al, 2007), oo muujinaysa in ilkinku uu u shaqeynayo deltaFosB, BDNF wuxuu u adeegaa kaalin guud oo nafsaani ah oo taageera neuroplasticity kaas oo ka dhexjiray daroogooyinka khatarta ah si ugu dambeyntii loo dhiso dib-u-kicin habaysan oo khasab ah.

BDNF ayaa si wacan loo yaqaan si kor loogu qaado qaababka baaxadda loo yaqaan 'synaptic plasticity', sida horay iyo gaabis ah muddada dheer ee xooggan (LTP), iyo sidoo kale dhiirigelinta qaabaynta dendritic-ka (Bramham iyo Messaoudi, 2005). Farsamooyinka ka hooseeya waxa guud ahaan ah xoojinta isdhexgalinta farshaxanka waa kala duwanyihiin, waxaana ka mid ah xoojinta istiraatiijiga ah ee kor u kaca, sii kordhinta glutamate, iyo kor u qaadida signmaptic NMDA. Marka la eego farsamooyinkan gacanta, maahan wax la yaab leh in BDNF loo adeegsado habdhaqanka caadiga ah iyo xasuustiisa. Ku saabsan daroogada maandooriyaha, BDNF waxay dhexdhexaad u tahay awoodda sii kordheysa ee faafinta iskudhaca ee unugyada dopamine ee VTA oo ay soo saartay maamulka cocaine-ka soo noqnoqota (Pu et al, 2006), iyo iyadoo la sii daayo maqaarka (Borgland et al, 2006), waxay gacan ka geysan kartaa taxadarro taxadar leh oo lagu eegayo LTP xooggan oo ku jirta unugyada dopamine ee VTA ka dib markii maamulka hal daroogo ah loo isticmaalo (si loo eego natiijooyinkaas iyo sida ay uga qayb qaadan karaan qaababka joogtada ah ee neuroplasticity ee hoos yimaada soo noqoshada, arag Jones iyo Bonci, 2005). Muhiimadda, heerka BDNF ee VTA, iyo sidoo kale NA iyo amygdala, si tartiib tartiib ah ayey u kordhisaa inta ay ka dheeraanayaan (Grimm et al, 2003). Korodhka koritaankan ayaa la qiyaasey inuu hoosta ka xariiqo kororka sii kordhaya ee daroogada-raadinta taas oo dhacda xilliga ka-goynta cocaine, oo laga yaabo in ay dhacdo, qayb ahaan, kordhinta dopamin D3 soo-bandhigeeyeGuillin et al, 2001; Le Foll et al, 2005). Xaqiiqada ah in BDNF ay sare u kacday maamulka daroogada khatarta ah iyo sidoo kale wali sarreeya meelaha maskaxda ah ka dib marka la joojiyo dheeraadka ah waxay tilmaamaysaa borotiinkan oo ah musharaxa neuroplastic ee xasilloon oo gacan ka geysan kara helitaanka daroogada-raadinta, iyo fulinta daroogada-raadinta kadib muddooyinka xad dhaafka ah.

Transit Neuroplasticity oo la xidhiidha Maaddada Molecular ee Drug Action

Noocyo kale oo ku-meel-gaar ah ee neuroplasticity oo ay sababtay daroogooyinka la qabatimay ayaa sidoo kale lagu sharaxay. Si kastaba ha noqotee, marka loo eego D1-CREB-deltaFosB Waddada Isgaadhsiinta, dhacdooyinkan tilmaamaya ayaa si gaar ah u ah daawooyinka shakhsi ahaaneed. Tusaale ahaan, isbeddelka ku yimid daroogooyinka dopamine waxay la xiriiraan amphetamine-like psychostimulants (Xeerarka et al, 2002), GABA-A isbeddellada isbeddelka ayaa la xusay ka dib markii khamriga ba'an (Charlton et al, 1997), iyo nicotine waxay qabtaan daawooyinka nicotinic (Mansvelder iyo McGehee, 2000). Is-beddeladaas daroogada gaarka ah waxay ku-biirisaa daroogooyinka muhiimka ah ee daroogada, gaar ahaan, cudurrada joojinta waxay ka kooban yihiin sifooyin u gaar ah fasalka daroogada. Sidoo kale, isbeddelada daroogada gaarka ahi waxay saameyn ku yeelataa wareegga si muhiim u ah abaalmarinta caadiga ah iyo barashada daroogada. Guud ahaan, saameynta daawooyinka gaarka ah ayaa ka baxsan baaxadda dib-u-eegista hadda ee diirada saaraya waxa ka muuqda muuqaallada caamka ah ee la wadaago inta badan ama dhammaan daroogooyinka xadgudubka iyo mabda'a guud, ayaa sidoo kale lala wadaagaa dareemaha nafsaaniga ah.

Soo-koobidda Nuuriku-nacaybnimada Qaadashada Qaadashada Isticmaalka Maandooriyaha iyo Ku-meelgaarka ah ee Isticmaalka Daroogada Bulshada ee ku-Xakameysan

Jaantuska 4 waxay muujinaysaa qaybo kala duwan oo ku lug leh neuroplasticity oo la xidhiidha isticmaalka soo noqnoqda ee daroogada la qabatimay iyo ka-dhaafitaanka xiga. Waxaa muhiim ah in la ogaado in tijaabooyinka ay sameeyeen maamulka maskaxda ee soo noqnoqda, iyo in ay ka yartahay min opioids, ay bixiyaan macluumaadka badankood ee hoos yimaada qaababka lagu muujiyay Jaantus 4a. Saddex qaybood oo guud ayaa la soo jeediyey. Qaybta ugu horreysa waxaa ka mid ah soo saarista unugyada dhaqdhaqaaqa-ku-tiirsan ee ay ku leedahay maamulka deg-degga ah, iyo horumarinta dulqaad-u-qaadista illaa ka-dib markii la soo celiyo maamulka. Qaybahaas waxaa ka mid ah C-fos, Arc, Homer1a, Neef, iyo Zif / 268. Waxaa muhiim ah, ka dib marka laga reebo mudaharaad, dulqaadka dulqaadashada iyo borotiinnadaas ayaa mar kale lagu daaweyn karaa daaweynta nafsaaniga ah ee nafsaaniga ah, badanaa heerarka ama qaababka muujinta ka duwan tan keentay soo-gaadhista daawada ugu horreysa. Barootinnadan waxaa loo maleynayaa in ay muhiim u tahay bilaabista neuroplasticity ee lagama maarmaanka u ah si loo helo dabeecado cusub, iyo dib-u-qaabeynta dabeecadaha la bartay, oo ay ku jiraan daroogada raadinta.

Qeybta labaad waxaa lagu gartaa borotiinno, kuwaas oo muujinaysa muujinaysa in si tartiib tartiib ah loo kordhiyo ama loo yareeyo daroogada soo noqnoqota, iyo in la joojiyo muddooyinka kala duwan ee ka-dhaafka ah. Laba qeybood oo kala duwan ayaa lagu muujiyay Jaantus 4b. Midka ugu horreeya waxaa ka mid ah isbeddelada borotiinka ee soconaya saacado illaa maalmo ka fogaansho iyo caadi ahaan u dhigma isbeddelada si dhow ula xiriira barta daawada ee tallaalka. Qeybta kale ee hoose waxaa matalaya isku ururinta deltaFosB, halkaas oo heerarka sare ay ku sii jiri karaan maalmo ama toddobaadyo. Qeybtan dambe ee hoose ayaa loo maleynayaa inay gacan ka geysaneyso helitaanka barashada dhiirigelinta, laakiin muhiimadda, ka jawaab celinta isticmaalka daroogada soo noqnoqda, deltaFosB waxaa lagu qiimeeyay inay dhexdhexaadiso kala-guurka isticmaalka daroogada bulshada ee isticmaalka soo noqoshada (Nestler, 2005).

Qeybta saddexaad waxaa ku jira borotiinno kor u kaca ama la yareeyey ka dib sii dheeraaday. Laba qaybood oo kala duwan ayaa loo tixgeliyaa Jaantus 4c. Marka ugu horeysa waxaa lagu calaamadiyaa BDNF oo ka soo jeeda gobollo maskaxeed ka dib markii maamulka maskaxda ee soo noqnoqonaya iyo kor uqaadkani sii socdo sii kordhaya mudada sii dheeraatay (Grimm et al, 2003; Lu et al, 2004a). Qaybta labaad ee qaybta labaad ayaa loo tixgelin doonaa faahfaahin hoose, waxaana ku jira borotiinka aan isbeddel lahayn inta lagu jiro maamulka daroogada, laakiin waxay sare u qaadaan ama yaraadaan muddada ay joogsadaan. Waxaa la saadaaliyay in qeybtaani ay ku jiraan dhacdooyin neuroplastic oo ay u badan tahay in ay masuul ka yihiin xaaladda ay u nugul yihiin dib u soo noqoshada. Inta badan isbeddeladaan is-beddelka ah lama muujin in ay dhacaan in lagu soo celiyo soo noq-noqoshada dareenka noolaha ee dhiirigelinta nafleyda waxaana laga yaabaa inay noqdaan kuwo nooloolayaal ah neuropathology ee qabatinka.

DHIBAATOOYINKA NEUROPLASTICITY WAXYAABO UU QAABILSAN YAHAY WAXYAABAHA WAXBARASHADA

Sida kor lagu sharaxay, marka dabeecadda loo qorsheeyay in la helo abaalmarin ama ka-hortagto natiijo xun oo la ogaaday, doorka dopamine isbeddelka mid ka mid ah dhiirigelinta barashada cusub mid ka mid ah awood u-helidda xogta la bartay si ay si wax ku ool ah u fuliyaan jawaab celinta habdhaqanka (Schultz, 2004). Taas bedelkeeda, gudbinta glutamate ee kortex iyo allocortex (sida, amygdala iyo hippocampus) ee wareegga gawaarida wadnaha (oo ay ku jiraan NA) waxay u muuqdaan kuwo muhiim u ah fulinta dabeecadda la barto (Kalivas iyo Volkow, 2005). Intaas waxaa dheer, waxaa loo maleynayaa in hab dhaqameedka si isdabajoog ah loo fuliyo, doorka gumaysiga corticophugal glutamate ee ka shaqeynaya PFC iyo amygdala NA, wuxuu noqonayaa mid aan muhiim aheyn oo ku salaysan glutamate mashruuc ka soo jiidashada gawaarida baabuurta dareenka qallalka ah (Everitt iyo Robbins, 2005). Habkan, habdhaqanku wuxuu kakoobayaa inuu yahay geeddi-socod caddeyn ah oo ku lug leh hawlaha fulinta horay u-qabashada habdhaqan caadi ah oo ka faa'iideysanaya wareegtada xasuusta shaqada (Barnes et al, 2005). Dhaqan ahaan, kala-guurkaan laga bilaabo cadaynta dabeecadaha tooska ah waxay ku habboonaan karaan in ay u oggolaadaan dabeecadaha si wanaagsan loo barto si ay si wax ku oolnimo ah u socdaan iyada oo aan la ogaanin kaqeybgalka, iyo haddii dhiirigelinta dhiirogelinta muhiimka ah ama macnaha isbedelka, hawlaha fulintu waxay ku-meel-gaar ah u tahay inay caqabad ku noqdaan caado ka dhigashada qayb cusub ku habboon isbedelka deegaanka. Marka laga hadlayo daroogada-raadinta, kala-guurka ka soo horjeeda xayawaanka horay u socodka wareegga gawaarida waxay muujinaysaa luminta xakamaynta iyo dib-u-dhac qasab ah. Waxaa muhiim u ah jiritaanka maandooriyaha, kartida horay u lahaanshaha, xuduudaha cadeynta ah ee ku lugta leh iyo khalkhal gelinta caadada daroogada raadinaysa ayaa daciif ah, taas oo ka dhigeysa in ay adagtahay go'aanka fulinta in uu ku dhaco daroogada-raadinta (Everitt iyo Robbins, 2005; Kalivas iyo Volkow, 2005). Fahmidda neurophysiology ee xoojiya isbedelkan isbedbedelka ah ee loo maro daroogada-raadinta qasabka ah, iyo daciifinta xakameynta xakameynta horay loo xakameeyay ee daroogada-raadinta waxay u baahan tahay fahamka neuroplasticka joogtada ah ee loo adeegsado isticmaalka daroogooyinka soo noqnoqda. Gaar ahaan, tani waxay ku lug leedahay isbeddelka is-gaarsiinta glutamate iyo soo-saarka hypofrontality ee u oggolaanaya daroogada-doonaya in ay sii wadaan iyada oo aan wax dhexdhexaadin ah (Jentsch iyo Taylor, 1999; Goldstein iyo Volkow, 2002).

Cudurka neuroplastic-ka ee xakameynta kortikal Glutamate: Nuuro-naqnimada dadka

Inta badan ee neuroplasticity ee xiniinyaha kortikal ayaa si toos ah loogu muujiyay in dadka isticmaala iyagoo isticmaalaya hababka kala duwan ee neuroimaging. Sidaa daraadeed, waxaa jira dhimista guud ee tallaabooyinka horay loo qabtey ee metabolismka iyo socodka dhiigga ee shakhsiyaadka lagu daro daroogooyin kala duwan, oo laga soo qaato kookeynta ilaa opioids ilaa khamriga (Goldstein iyo Volkow, 2002). Tani waxaa ka mid ah gobollada sida koreetka hore iyo kaniisad isbitaallada ah. Iyadoo loo eegayo iskaashiga u dhexeeya xayeysiinta bacriminta hore iyo ka shaqeynta dabeecadaha dhiirrigelinta dabeecada ee ku haboon (Buuxinta et al, 2002), iyo inta udhaxeysa kicinta xuddunta ama xakamaynta maskaxda iyo awoodda ay u leedahay inay bedesho habdhaqanka wanaagsan ee wax loo baddaley habdhaqanka la qabsiga (Kolb et al, 2004), khudbaddaani waxaa lagu tilmaamayaa inay tahay tilmaam xooggan oo awood u leh in la xakameeyo daroogada. Hoos-u-dhac ku yimaada xuubka xannuunka ee xiniinyaha ayaa sidoo kale lagu soo waramey in dadka daroogada loo isticmaalo ee daroogada ah (Franklin et al, 2002), laakiin lama ogaan haddii tilmaamahan iyo farsamooyinka astaamaha ah ee isku-dhafka (hypofrontality) uu yahay waxyaaba nuglaanta ah kahor intaan la isticmaalin kookeynta ama saameynta isticmaalka kiciyaha daba-dheeraaday. Arrin xiiso leh, markii la soo bandhigay cuna hore oo la xidhiidha isticmaalka daroogada oo sii xumaynaysa rabitaanka daroogada, waxaa jira calaamado firfircoon oo ku jira PFC, oo ay ka mid yihiin maqaayadda iyo xarumaha isbitaallada (ventral orbital cortices)Goldstein iyo Volkow, 2002; Wilson et al, 2004; Kalivas iyo Volkow, 2005). Daraasado badan, waxqabadka kordhay ee PFC ayaa si fiican u dhexmuuqday iyada oo la xoojiyay rabitaanka daraasadda ee daroogada. Sidaa darteed, kala duwanaanta ficilka horay udhexaadka ah ee udhexeeya heerka iyo heerarka kiciya amarrada daroogada waxay ka weyn tahay waxa ku dhaca maadada kantaroolka ee jawaab-celinta la xiriirta abaalmarinta bayoolajiga, sida habdhaqanka muuqaalka galmada. Intaa waxaa dheer, in la raaco cabashooyinka mukhaadaraadka lagu qeexay qayb ka mid ah jawaab celinta dhimista abaalmarinta nafleyda, marka cocaine addicts la soo bandhigay dhiirigelin galmo, firfircooni hor leh ayaa si weyn u liita marka la barbardhigo kontaroolada (Garavan et al, 2000). Dadaallada looga hortagayo wax ka qabashada jawaabaha cocaine ayaa sidoo kale lagu soo warramey in ay kordhiyaan dhaqdhaqaaqa xayawaanka hore (Dhallaanka et al, 2007), oo soo jeedinaysa in hawlaha cilladeysan ay ku dhici karto awood la'aanta inay ka soo hor jeeddo soo noqoshada.

Natiijo kale oo ka soo baxa daraasadaha neuroimaging oo tilmaamaya jawaab celinta hooseysa abaalmarinta bayoolajiga ee dadka la takooro waa hoos u dhaca dhaqdhaqaaqa dopamin ee dib u habeyn si loo yareeyo qiyaasaha hoose ee maskaxda (Volkow et al, 2004, 2005). Sidaas daraadeed, dopamine-ku-duufinta methylphenidate-ka oo lagu sii daayo striatum ayaa waxyeellada ku jirta daroogada cocaine ee ku saabsan maadooyinka. Sidoo kale, iyada oo aan loo eegin daroogada ugu badan ee lagu xadgudbo, ayaa dadka ku dhibaateeya waxay muujinayaan heerarka hoos udhaca D2 ee qanjidhada (Volkow et al, 2004). Inkastoo la yareeyo dukaamada D2 ee hoos u dhacaya waxay muujinaysaa qulqulka gudbinta dopamine, ma ahan wax la yaab leh in qofku soo sheego hoos u dhac ku yimaada ama raaxo leh si looga jawaabo methylphenidate marka loo eego maadooyinka. Taas bedelkeeda, halka methylphenidate ay ku adkaato jahwareer xoog leh oo ku jira daroogada, ma jirto wax xujo ah maadooyinka la barbardhigo. Si kastaba ha noqotee, maadooyinka aan kontoroolka ahayn ee isticmaala maandooriyuhu waxay ku kala duwan yihiin sida ay u cufnaanta D2 cufnaanteeda. Kuwa qaba dufka D2 ee hooseeya waxay soo saartaa saameyn wanaagsan oo wanaagsan oo laga helo methylphenidate, halka kuwa cufka D2 ka sarreeya aysan jeclayn saamaynta kiciyaha (Volkow et al, 2002). Natiijadan waxay ku saabsan tahay maaddooyinka caadiga ah ee bini'aadamka waxay la mid tahay natiijadii la midka ahaa ee astaamaha aadanaha (Nader iyo Czoty, 2005).

Isku soo wada duubista, baadhitaanada neerfaha waxay tilmaamayaan in ay isbeddelayaan isbeddelka wareegga maskaxda. Sidaa daraadeed, marka la eego xaaladda aasaasiga ah, tixgelinta ayaa ah mid aad u sarreeya dareenka dhiirigelinta nafleyda, sida caddaynta laba neurootigal, (1) waxqabadka hoos u dhaca ee PFC, iyo (2) hoos u dhigidda heerarka dhimirka ee Dopamin D2. Waxaa dhici karta in ay xitaa aad u muhiim u tahay baaritaanka xatooyada, awoodda dhaqdhaqaaqa bayolojiga ku habboon ee dhaqaajiya PFC waa waxyeello. Sidoo kale, farmashiyada ayaa sababtay sii-deynsashada dopamine ee striatum iyo dareenka suubban ee shakhsiyadeed ee sarreeya ama raaxada ayaa daciif ah. Si kastaba ha ahaatee, dareenka daroogada la xiriira ayaa si cad u dhaqaajinaya PFC ee dadka adduunka ku haboon oo ku xiran rabitaanka daroogada. Isku soo wada duub, xogta bukaan-jiifka ah waxay bixiyaan naqshadda nuucyada neurocircrery ee sifooyinka asaasiga ah ee takoorka; xad-dhaaf ah, ka-jawaab celinta daroogada, iyo saboolka ama aan habboonayn ka jawaabista dareenka noolaha ee muhiimka ah.

Dhibidda Nuuriku-darraanta ee Kortikal Glutamate Circuitry: Model Animals

Si aad u fahamtid aasaaska cellular ee sida isbeddelada ku dhacay wareegga corticolimbic iyo rajeynaya in la ogaado hababka loo marayo ama looga soo horjeedo isbeddellada, waxaa lagama maarmaan ah in la isticmaalo noocyada xayawaanka, taas oo u oggolaanaysa falanqayn farsamo oo badan. Muhiim u ah, xayawaanka iskood ayay u maareeyaan daroogada kuwaas oo u adeegsanaya bini-aadanka, iyo wareegga wareegga ah ee ka soo iibsashada dopamine-ku-tiirsan ee daroogada-doonaya in lagu fuliyo daroogada ku-xiran daroogada-raadinta ayaa muujinaya daraasadaha xayawaanka.

Nooca ugu badan ee loo shaqeeyo dib-u-soo-kabashada waxaa ku jira jimicsi tababbar si uu iskiis u maamulo daroogo, isagoo xayawaanka ku khasbey in uu ka tago ama aan laheyn tababbar, kadibna dib u soo bandhigo xayawaanka si loo isticmaalo daroogada, calaamadaha si khaas ah loogu duubo bixinta daroogada, daroogada lafteeda (Epstein et al, 2006). Iyada oo laga jawaabayo dareenkaas, xayawaanka loo tababaray ayaa daaweyn doona daroogada-raadinta xitaa haddii uusan jirin helitaanka daroogada.

Baadhitaankii hore ee dib u soo noqoshada xayawaanka ayaa ku lug lahaa isticmaalka jiirka jilicsan ee lagu daweeyo naloxone ama naltrexone. Abaalmarinta furfuran ayaa la xakumay kadibna markii kordhay bilowgii jawaabta, hoos u dhac degdeg ah ayaa dhacay (Davis iyo Smith, 1974). Dhawaan dhowaan, isku-dhafka khamriga ayaa la ogaaday in uu ka shaqeynayo habka istiraatiijiga ah ee loo yaqaan 'opioid' kaasoo soo saaraya dopamin dheellitiran ee NA iyo khamriga doonaya xayawaanka (Gonzales iyo Weiss, 1998). Raashin loo tababaray in ay is-maamulaan aalkolada kadibna la siiyo naltrexone waxay muujinaysaa joojinta kororka dopamine ee NA iyo joojinta is-maamulka aalkolada. Tusaalahan tooska ah ee cilladahan waxaa lagu qallajiyaa aalkolada aadanaha oo soo sheegta abaalmarinta caanaha ama maqnaanshaha khamriga marka la daaweeyo naltrexone (Volpicelli et al, 1995).

Dhawaan dhowaan, inactivation of nuclei kala duwan oo qaba qaba agagaaraha GABA ama xayiraadaha xakamaynta waxqabadka, maskaxda nuclei lagama maarmaan u ah in la dilo daroogada-raadinta ayaa la duubay (McFarland iyo Kalivas, 2001; Eeg, 2002; McFarland et al, 2004). Natiijooyinka daraasaddan lagu sameeyay tobankii sano ee la soo dhaafay waxay si aad ah ula siman yihiin daraasadihii hore ee sawirrada dadka. Qaybta ciriiriga ah ee wadnaha ah waa gobolka maskaxda ee lagu muujiyay inay tahay waajibaad iyada oo aan loo eegin habka loo xaddidayo daroogada-raadinta, ama joogitaanka ama maqnaanshaha tabar-darrada. Tani waxay qeexeysaa ka qayb qaadashada habka mashiinka mashiinka ah ee dabeecad fiican u tababaran sida daroogada raadinta. Dabeecad darro, haddii xooluhu aysan ku soconin tababarka, daroogada loo raadsado iyadoo lagu soo celinayo xayawaanka dib u soo celinta macnaha daroogada ma saameynayso kicinta qaab kasta oo maskaxeed oo caadi ahaan la xidhiidha barashada dhiirigelinta ama xayiraadda sababo la xidhiidha daraasad lagu sameeyo dareemayaasha (sida, meelaha ee PFC, amygdala, ama NA) (Fuchs et al, 2006). Si kastaba ha noqotee, haddii xayawaanku uu sii socdo tababarka, daroogada raadinta ee ay soo jiidanayaan calaamadaha, walbahaarka, ama daroogada laftiisu waxay ku lug leedahay wareegga intaa ka sii badan, oo ay ku jiraan wareega lagu aqoonsaday sawirka aadanaha. Tusaale ahaan, haddii tijaabo-yaqaanka maxaliga ah uu hortago mid ka mid ah nuclei ee wareegga taxan oo ay ku jirto saadaalinta dopamine ee VTA illaa PFC-da, saadaalinta glutamate ee PFC ilaa NA ama GABA / peptide saadaalinta ka soo baxa udubbeelka ventral pallidum (VP), daroogada-raadinta ee xayawaan la bakhtiiyay ayaa la xannibay. Sidaa awgeed, tababarku wuxuu ku fashilmaa gobollada maskaxda ee ku lug leh wax-qabad badan oo dareen-celin ah oo ku saabsan hab-dhaqanka raadsashada daroogada (McFarland iyo Kalivas, 2001; Eeg, 2002; McFarland et al, 2004), taas oo muujinaysa fekerka habdhaqanka guud ee akhlaaqda. Iyadoo lala xiriirinayo tabarucda keenaysa xakamaynta akhlaaqda, xaddiga daroogada raadsata (sida, cadaadis adag) oo ay sababtay xaaladda daroogada ee xayawaannada cayayaanka ayaa ka sarreeya daroogada raadinaysa xayawaanka la bakhtiiyay (Fuchs et al, 2006). Wadajir ahaan, wareegga iyo xogta akhlaaqda ayaa muujinaya in wareegga baaxadda leh ee la xidhiidha daroogada-raadinta ee maaddooyinka la bakhtiiyay ay u adeegsadaan inay nidaamiyaan daroogada raadinta. Taageeridda suurtogalnimada, in la yareeyo tababarka ayaa hoosta ka xariiqaya hoosaadyada GluR1 iyo GluR2 glutamate oo ku yaala NA ee jiirka kookaha ku tababaran (Sutton et al, 2003). Sidoo kale, tababarka xayiraadda xayawaanka cabsida leh waxaa loola jeedaa dhaqdhaqaaqa kortexsanaanta ciriiriga ee mashruuca NA (Sierra-Mercado et al, 2006). Sidaa darteed, sida faragelinta nafsaani-bulsheed ee dadka ku takhasusay inay ku soo celiyaan xukunka fulinta ee ku saabsan caadooyinka daroogada-raadsashada, tababarka xayawaanku waxay ku faaftaa xayawaan horay loo sii kobciyay oo beddelaya daroogada-raadinta ee jawaab-celinta calaamadaha, walbahaarka, ama daroogada lafteeda.

Xayndaabyada ku jira xayndaabka hore ee u dhexeeya xayawaanka daawada loo isticmaalo iyo muusikada bini-aadanka ayaa sii dheer iyadoo sare u qaadaysa sare u qaadista glutamate inta lagu guda jiro daroogada la raadinayo. Sidaa darteed, jiirarka loo tababaray in ay is-maamulaan cocaine ama herooin ayaa muujinaya koror calaamadeyn ah ee sii deynta glutamate ee NA ee ka jawaabista daroogada-ama daroogada-raadsashada daroogada (McFarland et al, 2003, 2004). Intaa waxaa dheer, kororkan ayaa la baabiiyay iyadoo la mamnuucay PFC-ta, oo aan ku jirin labadii suntan ee la shiiday ama la mamnuucay kokaininka ama herooin. Si kale haddii loo dhigo, iyada oo aan loo eegin maamulka daroogada ee soo noqnoqonaya, haddii xayawaanku aysan ku lug laheyn dabeecadaha daroogada lagu raadinayo ma jiraan wax la yiraahdo sii-deyn la'aanta glutamate synaptic. Sidaa awgeed, maamulka daroogada khatarta ah kaligeed kuma filna in la dhaqaajiyo waddada hore ee loo yaqaan glutamate pathway, halkii waddadani waxaa lagu qoraa xayawaanka barashada shaqada daroogada. Waxaa muhim ah, kororka glutamate ayaa lagu arkay inta lagu jiro cunto-raadinta xayawaanka lagu tababaray naf-ahaanshaha cuntada, taas oo muujinaysa in neeroblitnaantaas aan lagu dhejin doonin inay bartaan abaalmarinta nafleyda (McFarland et al, 2003). Taageerida muhiimada ay leedahay ka-fadhiisinta glutamate ee daroogada raadinta daroogada, gudida galmada ee glutamate antagonists ayaa ka hortageysa daroogada raadsashada, sida ka-hortagga PFC (Cornish iyo Kalivas, 2000; Di Ciano iyo Everitt, 2001). Dhawaan, qaar ka mid ah neuroplastic-ka molecular-ka dhexdhexaadinta dib-u-dhigista horudhaca horay loo yaqaan 'glutamate' ee NA ayaa la darsay. Waxaa intaa dheer, cawaaqib xumada ka dhalatay sii-deynta kaluumeysiga inta lagu jiro muddada daaweynta daroogada ayaa la baaray.

Neuroplasticity Waxay gacan ka geysataa Gudbinta gudbinta Glasamat ee Dysregulated

Iyadoo sii-deynta sii-deynta glutamate uu sii socdo, bacriminta midab-dhiska ayaa sidoo kale sii jiraya. Furaha ka midka ah qalabka isbeddelka ah ee hoos u dhigma waa hoos u dhigidda is-beddelka cystine-glutamate (xc-) (Baker et al, 2003). xc - waa tallaabo xaddidan oo xaddidan oo unugyada ku dhaca cystine si ay u sameeyaan antioxidant glutathione intracellione, waxayna dhacdaa iyada oo isweydaarsiga kor u qaadista hal cystine ah oo lagu beddelayo sii deyn hal maadi ah oo ku jirta glacamate intracelular glutamate ah meel bannaanMcBean, 2002). Caadi ahaan, sii-deynta this nonsynaptic glutamate waxay keenaysaa heerarka heerkulka ka baxsan xayawaanka ku filan si loo kiciyo habka daaweynta maaddada 'metabotropic glutamate glucamate autoreceptors' (mGluR), oo sidaas lagu sii daayo fasiraadda "glutamate synaptic glutamate"Moran et al, 2005). Si kastaba ha noqotee, hoos u dhac ku yimaada NA ka dib cocaine-ka joogtada ah ayaa ka saaraya xakamaynta tani, taasoo kordhinaysa suurtogalnimada sii deynta glutamate. Hoos udhaca tani waxaa lagu dhejiyaa hoos u dhigista mGluRs, oo loo maleynayo inay ka dhalanayso fosforyaalka kororka (Xi et al, 2002), iyo soo saarista borotiinka loo yaqaan activator of G-protein signin 3 (AGS3), kaas oo u adeega xaddidaadda calaamadaha soo-galinta ee loo marayo Kiα fasalka G protein (Bloom iyo Lanier, 2003; Bowers et al, 2004; Yao et al, 2005). Xiriirkani waxaa lagu muujiyey gudaha Jaantuska 5.

Daraasad lagu sii daayo oo lagu sii daayo glutamate synaptic inta lagu jiro marxaladaha daroogada ee soo noqnoqda ayaa loo maleynayaa in ay gacan ka geystaan ​​tiro badan oo ah isbeddelada postsynaptic. Qayb ka mid ah kuwan waa isbeddellada si wanaagsan loo aasaasay ee cufnaanta lafdhabarta ee lagu arkay NA iyo goobaha horay loo xannibay ka dib markii la isku daro daawooyinka la qabatimay (Robinson iyo Kolb, 2004). Waxaa si fiican loo asaasay in la isticmaalo glutamate in qanjidhada dhaqanka ee isbeddelka cufnaanta lafdhabarta, midba kor u kaca ama hoos loo dhigo iyada oo ku xiran xaddiga kicinta glutamate ee qaboojiyaha iyo laga yaabo in ay hoos u dhigto (Lippman iyo Dunaevsky, 2005; Richards et al, 2005). Sidaa darteed, waxaa laga yaabaa in aan la yaabin in ay ku xiran tahay daroogada oo si joogto ah loo maamulo, waxaa jira koror (maskaxiyan) ama hoos u dhaca (opioids) ee cufka dhabarka (Robinson iyo Kolb, 1999, 2004; Jedynak et al, 2007). Nidaamyada unugyada jirka ee aasaasiga ah ee neuroplasticity ee xakamaynta morphology waa aag cusub oo ka mid ah waxqabadka cilmi baarista aad u xoogan. Si kastaba ha noqotee, qawaaniinta loo yaqaan 'cytoskeleton' oo labadoodaba xasilin kara ama bedeli kara mawduucyada dhabta ah waa musharaxa rasmiga ah ee geedi socodka laga yaabo in uu hoos u dhaco cufnaanta dhabarka (Rao iyo Craig, 2000; Lisman, 2003; Blanpied iyo Ehlers, 2004; Matus, 2005). Sidaa awgeed, waxaa jira koror sii socda oo ku yimid baaskiil hawleedka ka dib markii uu ka soo tago maamulka maskaxda ee joogtada ah (Dhammaan et al, 2006). Korodhka baaskiilada hawleedku wuxuu dhacaa, ugu yaraan qayb ahaan, laga yaabo in la yareeyo Lim kinase, taas oo si adag u xakamaynaysa kaydinta F-actin, iyo sidoo kale kobcinta dhabarka (Meng et al, 2002; Soosairajah et al, 2005). Ka sokow wax ka beddelka wadnaha laf-dhabarta waxaa kale oo cawaaqib xumo ah in baaskiil wadista ficilku ay baddali karto tahriibinta borotiinnada xuubka postsynaptic (Kasai et al, 2003). In kasta oo aysan daruuri ahayn natiijada korodhka ficilka ee 'actin baaskiilka', isbedel suurta gal ah oo muhiim ah ka ganacsiga tahriibta postsynaptic waa koror waara oo ku dhaca galinta xuubka gulukhayaasha AMPA (Mangiavacchi iyo Wolf, 2004; Sun et al, 2005; Boudreau iyo Wolf, 2005). Si la yaab leh, si kastaba ha noqotee, kororka aqbaleyaasha AMPA waxay la xiriirtaa karti la'aan u horseedi kara niyadjab muddo-dheer ah (oo guud ahaan la xiriirta hoos u dhacayaasha AMPA-da)Martin et al, 2006). In kasta oo raadintaan dhowaan lagu muransan yahay daraasad muujineysa in ka dib markii ay ka baxdo maandooriyaha in ay jiraan koror muuqda oo ku saabsan AMPA ee hadda ku jira unugyada sumowga (Kourrich et al, 2007). Isku soo wada duuboo, cilmiga elektiroonigga ah ee la qabatinka maandooriyaasha unugyada 'unugyada lafdhabarta ayaa xilligan ah aagagga jahwareerka ku ah suugaanta (Kalivas iyo Hu, 2006).

Waxa xiisaha lihi, dhiirrigelinta soo-dhoweynta BDNF waxay dhiirrigelisaa baaskiil wadista ficil celiyana cufnaanta laf-dhabarka (Bramham iyo Messaoudi, 2005), oo tilmaamaysa in kor u qaadista kor u kaca ah ee BDNF inta lagu jiro ka bixitaanka ay si toos ah ugu biirin karto laqabsashada joogtada ah ee gudbinta xad dhaafka ah. Iyada oo khilaafsan aragtidaas, dhiirrigelinta dhakhaatiirta BDNF ee kaydadka ayaa kor u qaadda raadinta cocaine (Graham et al, 2007), saameyn ayaa sidoo kale keentay asagoo joojinaya ficilka baaskiil wadista ee NA (Dhammaan et al, 2006). Si kastaba ha noqotee, daraasad dhowaan la sameeyay ayaa shaaca ka qaaday in siidaynta BDNF galay qasnadaha kadib markii maamulka loo galay PFC ay ka hortageen labadaba daroogada ay keentay dawada iyo sii deynta "glutamate" ee la xidhiidha raadinta cocaine (Berglind et al, 2007). Waxaa la isla dhex marayay in BDNF ee loo maamulo PFC si aadaabtakoor leh loosii daayay loona sii daayo NA si ay u soosaarto dhaqankan dabeecadeed (Altar et al, 1997). Sidaas awgeed, sii-daynta 'BDNF' ee ka-hortagga afafka hore ee loo maro NA ayaa laga yaabaa inay soo saarto saamayn ka duwan tan tirada dawooyinka loo isticmaalo microinjecting.

In kasta oo adkaysiga neuroplasticity ee NA iyo striatum laga yaabo inay muujiso hypofrontality ee lagu arkay qabatinka 'neuroimaging addicts', waxaa loo qaadan karaa in waarida neuroplasticity sidoo kale ay si toos ah uga dhacdo PFC. Runtii, maareynta maskaxda ee soo noqnoqda waxay kordhisaa cufnaanta laf dhabarta unugyada hore ee unugyadaRobinson iyo Kolb, 2004). Marka la barbardhigo unugyada laf-dhabarka ee unugyada halkaas oo kororka cufnaanta laf-dhabarta ay la xiriirto dheecaan ka hooseeya xuubka maskaxda (Zhang et al, 1998), unugyada muraayadaha hore ee hore u muuqda kuwo si fudud lagu kicinayo (Dong et al, 2005). Tani waxay la mid tahay kororka weyn ee glutamate synaptically lagu sii daayay NA ee la soo saaray xilligii dawada-raadinta, waxaana laga yaabaa, qayb ahaan, inay la xiriirto neuroadaptations-ka gacanta sida calaamadaha oo hoos loo dhigo iyada oo loo marayo soo-dhaweynta Gi-lammaaneed sababtuna ay tahay kororka AGS3 (Kalivas et al, 2005). Sidaas awgeed, halka isbeddelada soo-dhoweynta dhexdhexaadinta D2 ee firfircoonaanta firfircoonaanta unugyadu ay u muuqdaan kuwo liidan ka dib markii ay ka baxeen kaabayaasha daba-galka ah, saameynta firfircoon ee ay kujiraan Gs-coupled D1 receptors are morement (Nogueira et al, 2006). Tani waxay gacan ka geysan kartaa kor u qaadista xaddiga xuubka iyo luminta xuubka xuubka ee laga soo sheegay neurons-ka hore ka dib cocaine-ka daba-dheer (Trantham et al, 2002), maaddaama D1 receptor kicinta lagu dhiirrigelinayo galinta xubinta AMPA ee xuubka (Sun et al, 2005). Xaqiiqda ah in kicinta D1 receptor ee PFC loo baahan yahay dib-u-soo-nooleynta daroogada ayaa la jaan qaada suurtagalnimada tan (Xarkaha et al, 2003; Sun iyo Rebec, 2005).

Soo Koobid Neuroplasticity Ku Saabsan Fulinta Meelmarinta Xeerka iyo Soo Celinta Khasabka Ah

Sida lagu muujiyey Jaantus 4c, noocyada neuroplasticity ee u adkaysta inta lagu jiro ka fogaanshaha waxay bixiyaan aaladda 'neuroplastic substrates' oo salka ku haysa u nuglaanshaha u nugulnaanta cudurka balwadda. Daraasado kaladuwan ayaa taageeray sii-deynta hor-u-ogolaanshaha glutamate-ka ee NA iyadoo loo yahay dhexdhexaadiye muhiim u ah raadinta daroogada. Sidoo kale, isbeddelada la calaamadeeyay ee calaamadda glutamate postsynaptic, oo ay ku jiraan isbeddelada ku dhaca dareemayaasha neerfayaasha jirka ayaa laga yaabaa inay gacan ka geystaan ​​isbeddelada. Caagagga gacantu ee salka ku haya labadaba hypofrontality muuqata markay tahay gundhigga iyo jawaabta adag ee PFC iyo wax soo saarkii NA inta lagu gudajiray raadinta daawada ama rabitaanka daroogada ayaa bilawday inay si buuxda u muuqato iyo, sida hoos lagu qeexay, waxay ka kooban tahay goobo cusub oo suurtagal ah oo wax looga qabanayo horumarinta dawooyinka dawooyinka ee lagu daweeyo qabatinka.

TILMAAMAHA MUSTAQBALKA IYO MACLUUMAADKA DHAQANKA

Markaan sare u qaadno fahamkeenna hababka wareegga iyo mobilada kaas oo soo noqnoqoshada qaadashada daawada ay kordhineyso u nuglaanta soo noqoshada, bartilmaameedyada daroogada ee cusub ayaa imaan kara. Sida wareejinta nugul ee udhaxeysa dib-u-habeynta iyo qasab noqoshada ay awood u siineyso caqliyadaha horumarinta dawooyinka cusub, iyo sidoo kale kordhinta fahamka siyaabaha daawooyinka loo hagaajin karo natiijooyinka daaweynta nafsaani-bulsho.

U beddelashada khasab ah oo ku saabsan dib u soo celinta sharciga

Adeegsiga dawooyinka dawooyinka si loo fududeeyo awoodda balwadaha si loogu daro caddayn dheeraad ah, habsocodka go'aan qaadashada ee soo noqoshada ayaa muhiim u ah yareynta soo noqoshada khasabka ah. Sida kor lagu soo sheegay, kala-guurka dib-ula-noqoshada oo noqo caado ku saleysan miyir-beelka shaqada miyir-la’aanta ayaa ku lug leh luminta sharciyeynta hore. Daawooyinka qaar ee xadgudubka waxaa tan lagu muujiyaa cilado garasho ee howlaha la xiriira feejignaanta, jiidashada iyo awoodda ay wax uga beddeleyso dabeecadda ku saleysan macluumaadka cusub. Iyada oo ku saleysan natiijooyinkaan, daawo-sifeynteedka caadiga ah ama ka-hortagga neuroplasticity ee lagu soo saaray PFC si loo habeeyo dabeecadda hab-dhiska ayaa u muuqan doonta qaab qiimo leh. Sida kor lagu soo sheegay, isbeddelada molikalku waxay ku jiraan hoos udhac muuqata oo ah abaalmarinta bayoolojiga iyada oo hoos loo dhigayo isu-gudbinta dopamine, iyo sare u qaadida hor u-qaadista gudbinta isu-gudbinta 'glutamate' si ay horay ugu sii wado raadinta daroogada. Sidaa darteed, daawooyinka wax ka beddelaya gudbinta dopamine, gudbinta glutamate ama gudbinta GABA ayaa ah musharrixiin suuragal ah. Waxaa intaa dheer, saadaasha GABA ee NA waxaa lagu daboolay noocyo badan oo neuropeptides ah (McGinty, 2007), iyo peptides-kaan, iyo kuwa kale ee ku jira corticolimibic sidoo kale waxay u sharraxan yihiin daroogada.

Dopaminergics

Gudbinta Dopamine waxaa lagu sameeyaa isbeddelo kaladuwan iyadoo ku xiran nooca soo dhoweynta qaataha. Sidaa daraadeed, waxaa jira hoos udhaca calaamadaha receptor D2 (Volkow et al, 2004), koror suurtagal ah oo ku saabsan calaamadaynta D1 (Kalivas et al, 2005), iyo sare u qaadis calaamadaysan oo ku taal dadka qaata D3 taas oo sabab u ah kororka joogtada ah ee BDNF (Neisewander et al, 2004). Tani waxay adkeyneysaa saadaalinta sida ugu wanaagsan ee loo beegsado gudbinta dopamine. Si kastaba ha noqotee, waxaa jira xog aad u sarreysa oo heer sare ah oo taageerta adeegsiga kooxaha iska soo horjeeda ee D3 si ay u horjoogsadaan raadinta daroogada (Xi et al, 2006).

Glutamatergics

Iyada oo ku saleysan neuroplasticity ee kor lagu soo sheegay, xannibaadda sii deynta synaptik glutamate ee la xiriirta raadinta daroogada waxay umuuqataa inay tahay hab wanaagsan oo lagu yareyn karo niyadda ku soo laabashada. Si kastaba ha noqotee, suurtagal ma ahan in la isticmaalo kahortagayaasha buuxa ee soo dhoweynta ionotropic glutamate-ka dartood oo ay ugu wacan tahay waxyeelada aan la aqbali karin. Sidaas awgeed, habab kala duwan oo dawooyinka ah ayaa u soo ifbaxaya wax ka beddelidda halkii ay ka horjoogsan lahaayeen gudbinta glutamate-ka. Qaar ka mid ah xeryahooda ayaa mar hore galay tijaabooyin caafimaad oo waxay muujiyeen wax ku ool yar. Tusaale ahaan, acamprosate iyo topiramate waxay leeyihiin ficilo daciif ah oo ka soo horjeedda soo dhoweynta AMPA (Myrick iyo Anton, 2004; Cubells, 2006). Topiramate ayaa la sheegay inay yareynayso soo noqoshada maandooriyaha kocaine (Kampman et al, 2004). Sidoo kale, modafinil iyo N-acetylcysteine ​​ficil ahaan si loo kordhiyo glutamate-ka extracellular-ka oo markaa dhiirrigelinta mGluR-inhibition ee sii-deynta 'synaptic glutamate' ayaa muujisay wax ku oolnimada soo-noqoshada maandooriyaha ama damaca hunguriga, siday u kala horreeyaan (Dackis et al, 2005; LaRowe et al, 2007). Saddex sheybaar oo madax-bannaan ayaa soo wariyay (Dackis, 2004; Malcolm et al, 2006; Hart et al, 2007) in modafinil uu yareeyo kookaha si aad u sarreeya iyadoo la kordhinayo kordhinta glutamate-ka 'extracellular glutamate' iyo firfircoonida xannibaadda mGluR sida kor lagu sharaxay. Waxaa intaa dheer, moodooyinka caadiga ah, mGluR2 / 3 agonists ayaa la muujiyay inay horjoogsanayaan raadinta daroogada (Baptista et al, 2004; Peters iyo Kalivas, 2006).

GABAergics

Moodooyinka hore ee loo yaqaan 'cocaine' iyo 'heroin' ayaa muujinaya in hoos u dhac ku yimid sii daynta GABA ee loosoo gaabiyo VP ay soo bandhigto NA wax ku saabsan arrimaha la xiriira daroogada (Caille iyo Parsons, 2004; Taang et al, 2005). Taageerida muhiimada laqabsashadan, dawooyinka dhiirrigeliya gudbinta GABA waxay muujiyeen ballanqaad daraasado caafimaad iyo mid caafimaad, vigabatrin (inhibitor of transferase GABA), gabapentin (makaanikada), iyo baclofen (GABAb agonist). Akhristaha waxaa loo tixraacaa dulmarradii ugu dambeysay ee ku saabsan adeegsiga GABAergics ee lagu daaweynayo balwadda maandooriyaha (O'Brien, 2005; Vocci iyo Ling, 2005).

Peptidergics

Qaar badan oo neuropeptides ah ayaa lagu gartaa GABA saadaasha ka socota NA, oo ay ku jiraan neurotensin, walaxda P, dynorphin, iyo CART (McGinty, 2007). In kasta oo aqoonteenna ku aaddan sida ay kuwani wax u tarayaan ama aysan u xakameynin maareynta daroogada ee ay dhexdhexaadiyeen kuwa ka soo horjeedda saadaasha pallidum waa mid aad u liita, haddana waxaa la muujiyey in xannibidda dadka loo yaqaan 'Enkephalin receptors' ee VP ay ka hortageyso raadinta cocaine qaababka xayawaanka (Taang et al, 2005), wax saameyn ah oo gacan ka geysanaysa isticmaalka naltrexone ee qabatinka ethanol (Vocci iyo Ling, 2005).

Gabagabada

In kasta oo ay jireen horumarro muhiim ah oo ku saabsan fahamkeenna neuroplasticity ee salka ku haysa horumarka balwadda iyo u nuglaanta u nuglaanta soo noqoshada, waxaan ku jirnaa marxalad aad u liidata markii aan awood u leenahay inaan ku dabaqi karno aqoontan cusub si loogu daaweeyo dadka balwada leh. In kasta oo aan haysanay qaar ka mid ah murashaxiinta dawooyinka u leh xakameynta neurotransmission ee neurons-ka ee loo yaqaan 'circuitry' ee muuqaalka lagu muujiyey inuu yahay mid muhiim ah, way adag tahay in la xakameeyo neuroplasticity-ka oo lagu soo saaray calaamad muujinaysa murugada taasoo muhiim u ah balwadda. Adeegsiga macluumaadkan cusub waxay sugeysaa sameynta xeryayaal xulasho loogu talagalay borotiinnada bartilmaameedka ah ee dariiqyada tilmaamaya, iyo tan ugu muhiimsan, macnaheedu waa bixinta xeryahooda. Si kastaba ha noqotee, qaababka loo yaqaan 'neuroplasticity' ee la aqoonsaday ilaa maantadan la joogo ayaa tilmaamaya habka loo wajahayo daaweynnada mustaqbalka ee soo bixi doona markii tikniyoolajiyaddu ay soo socoto.

Notes

SHAQADA

Dr O'Brien wuxuu la taliye u soo noqday seddexdii sano ee la soo dhaafay Alkermes, Cephalon, Forest iyo McNeil Laboratories. Dr Kalivas ma haysto wax uu shaaca ka qaado.

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