Methamphetamine waxay wax ka qabtaa subpopulations of neurons regulating ku dhaqanka galmada ee jiirka lab (2009)

Neuroscience 2010 Mar 31; 166 (3): 771-84. doi: 10.1016 / j.neuroscience.2009.12.070. Epub 2010 Jan 4.

Frohmader KS, Wiskerke J, Wise RA, Lehman MN, Coolen LM.

source

Waaxda Nadaamka iyo Qalabka Galka, Dugsiga Schulich ee Daawada iyo Dentistry, Jaamacada Western Ontario, London, ON, Canada, N6A 5C1.

aan la taaban karin

Methamphetamine (Meth) waa kicis heer sare ah. Ku xadgudubka Meth ayaa badanaa lala xiriiriyaa dhaqanka khatarta galmada iyo kororka kordhinta fayruska 'Human Immunodeficiency Virus' iyo dadka isticmaala Meth waxay soo sheegaan rabitaanka galmada, kacsiga, iyo raaxada galmada. Habka bayoolajiga ah ee loogu talagalay nexus-ku-galmoodkani lama garanayo. Daraasadani waxay muujinaysaa in maamulka Meth ee ragga labka ah ay ku kiciyaan nuuroonnada gobollada maskaxda ee nidaamka mesolimbic ee ku lug leh xeerka habdhaqanka galmada. Gaar ahaan, Meth iyo wadaagida unugyada iskubeddada ah ee nucleus waxay soo saartaa xudunta iyo qolofka, amygdala basolka ah, iyo kortex duuban. Natiijooyinkaasi waxay muujinayaan in liddi ku ah dawooyinka la rumaysan yahay ee xad-gudubka ah ay awood u yeelan karaan unugyada isku midka ah sida dabiiciga dabiiciga ah, taas oo ah dabeecad galmo, iyo sidoo kale waxay saameyn ku yeelan kartaa raadinta khasaaraha dabiiciga ah.

Keywords: nucleus accumbens, amygdala baslin ah, kortex hore, daroogo maandooriye, dhalmo

Dhiirigelinta iyo abaalmarinta waxaa nidaamiya habka mesolimbic, shabakad isku xiran oo ka mid ah aagga maskaxda oo ay ka kooban tahay wareegga wareegga ah ee VTA nucleus (NAc), amygdala gogol-galka ah, iyo maafiyada hore ee maafiyada (mPFC)Kelley, 2004, Kalivas iyo Volkow, 2005). Waxaa jira caddaymo dhab ah in nidaamka mesolimbicku uu ku shaqeeyo si wax looga qabto labadaba waxyeelada xadgudubka (Di Chiara iyo Imperato, 1988, Chang et al., 1997, Ranaldi et al., 1999) iyo si dabiici ahaan loo abaalmariyo dabeecadaha sida dhaqanka galmada (Fiorino et al., 1997, Balfour et al., 2004). Habdhaqanka galmada, iyo gaar ahaan jilicsanaanta, waa mid aad u fiican oo xoojinaya xayawaanka (Pfaus et al., 2001). Jiirka jinsiga wuxuu abuuraa doorbid boos oo xaalad ah (CPP) si loo kantaroolo (Agmo iyo Berenfeld, 1990, Martinez iyo Paredes, 2001, Tenk, 2008), waxayna fulin doonaan hawlaha hawlaha si ay u hellaan galmada haweenka qabta ah (Everitt et al., 1987, Everitt iyo Stacey, 1987). Daroogooyinka xadgudubka ayaa sidoo kale abaalmarin iyo xoojin, iyo xayawaanka ayaa baran doona is-maamulida walxaha xadgudubka, oo ay ku jiraan opiates, nicotin, khamriga iyo nafsiyaadka dhimirka (Xigmad, 1996, Pierce iyo Kumaresan, 2006, Feltenstein iyo Arag, 2008). Inkasta oo la og yahay in daroogada xadgudubka iyo habdhaqanka jinsiga labadaba ay u dhaqdhaqaaqaan goobaha maskaxda maskaxda, haddana hadda ma cadda in haddii daroogooyinka xadgudubku ay saameyn ku yeeshaan muruqyada isku midka ah ee dhexdhexaadinta dhaqanka galmada.

Cilmi-baarista maqalku waxay muujiyeen in cuntada iyo daroogada ay kiciyaan nuucyada NAc. Si kastaba ha noqotee, labada gacan-qabeyaal ma sameeynayaan unugyada isku midka ah NAc (Carelli iyo al., 2000, Carelli iyo Wondolowski, 2003). Intaa waxaa dheer, cuntada iyo isweydaarsiga isku-dhafka ah ma keenaan isbeddel dheer oo ku yimaada guryaha electrophysiological taas oo ay sababtay kocaine (Chen et al., 2008). Taa bedelkeeda, ururinta caddayntu waxay soo jeedinaysaa in dabeecada galmada iyo daawooyinka xadgudubku ay dhab ahaantii u dhaqmi karaan isla maskaxyada mesolimbic. Cilmi-nafsiyeedka iyo opioids ayaa bedelaya muujinta dhaqanka jinsiga ee jiirkaMitchell iyo Stewart, 1990, Fiorino iyo Phillips, 1999a, Fiorino iyo Phillips, 1999b). Xogta dhowaan laga helay shaybaarkayagu waxay muujisay in waayo-aragnimada galmadu ay bedesho jawaabta maskax-yareeriyeyaasha sida lagu caddeeyey jawaab-celinta laf-dhabarta iyo dareemidda abaal-marinta d-amphetamine ee xayawaanka (Pitchers et al., 2009). Jawaab isku mid ah ayaa hore loo arkay iyada oo soo noqnoqonaysa soo noqnoqoshada amphetamine ama daroogooyinka kale ee xadgudubka (Lett, 1989, Shippenberg iyo Heidbreder, 1995, Shippenberg et al., 1996, Vanderschuren iyo Kalivas, 2000). Wadajir ahaan, natiijooyinkani waxay soo jeedinayaan in habdhaqanka galmada iyo jawaabaha daroogada xadgudubka ay dhexdhexaadinayaan qanjirro isku mid ah oo ku yaal nidaamka mesolimbic. Sidaa darteed, ujeedada ugu horreysa ee daraasaddan soo socota waxay tahay in la baaro nadaamka neerfurka ee habka maskaxda ee habka galmada iyo maamulka daroogada xayawaan isku mid ah. Gaar ahaan, waxaan tijaabinay sharaxaadda in miyir-beelka, methamphetamine (Meth), si toos ah u dhaqangaliso qanjirrada sida caadiga ah dhexdhexaadiya dhaqanka galmada.

Meth waa mid ka mid ah daroogooyinka sharci darrada ah ee adduunka (NIDA, 2006, Ellkashef et al., 2008) iyoIn badanaa lala xiriiriyo habdhaqanka isbeddelka galmada. Si xiiso leh, dadka isticmaala meth ayaa soo sheega rabitaanka galmada iyo jimicsiga, iyo sidoo kale farxad galmo xoojiyay (Semple et al., 2002, Schilder et al., 2005). Intaa waxaa dheer, Ku xadgudubka Meth ayaa caadi ahaan lala xiriiriyaa habdhaqanka galmada (Rawson et al., 2002). Isticmaalayaasha badanaa waxay soo sheegaan in ay leeyihiin lamaanayaal badan oo galmo ah ayna u badantahay in ay isticmaalaan difaac marka loo eego kuwa kale ee daroogada isticmaala (Somlai et al., 2003, Springer et al., 2007). Nasiib darro, daraasado muujinaya in Meth ay u adeegsato saadaaminta habdhaqanka khatarta galmada waxay ku xadidan yihiin iyaga oo ku tiirsan is-sheegis aan la xaqiijin (Elifson et al., 2006). Sidaa daraadeed, baaritaan ku salaysan qaabka taleefanka ee isbeddelka Meth ee ku yimid dabeecadaha galmada ee qaabka xayawaanka ayaa looga baahan yahay fahamka this daroogada galmada daroogada adag.

Marka la eego caddaymaha kor ku xusan ee soo jeedinaya in daroogooyinka xad-gudubka, gaar ahaan Meth, laga yaabo inay u dhaqmaan qanjirrada sida caadiga ah ku lug leh dhexdhexaadinta dhaqanka jinsiga, ujeeddada daraasaddan xaadirka ah waxay tahay in lagu baaro dhaqdhaqaaqa maskaxda ee habdhaqanka jinsiga iyo maamulka methosimulant Meth. Daraasadani waxay hirgelisay farsamada neuroanatomical, iyadoo la adeegsanayo muuqaalka immunohistochemical ee jinsiyada hore ee hore iyo Fosforylated Map Kinase (PERK) si loo ogaado dhaqdhaqaaqa nucubka ah ee dabeecada galmada iyo Meth siday u kala horreeyaan. Foosto ayaa lagu muujiyay oo keliya gudaha nukleus ee unugyada, iyadoo leh heerar dherer ah oo muujinaya 30-90 daqiiqado kaddib marka lagu kiciyo neuronka. Waxaa jira caddeyn ballaadhan oo ah in dhaqdhaqaaqyada galmada ay ku dheehan tahay fosho maskaxeed (Pfausus iyo Heeb, 1997, Veening iyo Coolen, 1998), oo ay ku jiraan nidaamka nidaamka maskaxda (mesocorticolimbic) (Robertson et al., 1991, Balfour et al., 2004). Waxaa sidoo kale jira caddayn ah in daroogooyinka xadgudubka ah ay keenaan faahfaahin cadeyn ah oo ku saabsan habka maskaxda ee loo yaqaan 'mesocorticolimbic' (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005). Marka la barbardhigo falsafada Fos, fosforyelka ERK waa nidaam aad u firfircoon isla markaana wuxuu dhacaa kaliya daqiiqadaha 5-20 ka dib marka lagu daro dhaqdhaqaaqa neuronal. Foosaska Fos iyo PERK oo kala duwan ayaa ka dhigaya inay si fiican u calaamadiyaan jaangooyooyinka ku-meel-gaadhka ah ee laba-cirif oo kala duwan.

NIDAAMKA DHIBAATOOYINKA

maadooyinka

Xiddiga ragga ah ee Sprague Dawley (210-225 g) oo laga helay Charles River Laboratories (Montreal, QC, Canada) ayaa ku yaal laba baqshiile oo ah baqashada caadiga ah ee mooska (baqashada guriga). Qolka xayawaanka waxaa lagu hayaa 12 / 12 h wareega iftiinka iftiinka (nalalka off at 10.00 h). Cuntada iyo biyaha ayaa la heli karaa ad libitum. Dhammaan imtixaannada ayaa la sameeyay intii lagu jiray qeybtii hore ee mugdiga mugdiga ah ee hoosta ku yaal. Dumarka stimulus ee loo isticmaalo dabeecada galmada ayaa si xeeldheer u kordhay suuxdinta qoto dheer (13 mg / kg ketamine iyo 87 mg / kg xylazine) waxaana lagu siiyey maqaar-galaha subcutaneous oo ay ku jiraan 5% estradiol benzoate (EB) iyo 95% kolestaroolka. Soo dhaweynta galmada waxaa sababay maamulka subcutanous (sc) ee 500 μg progesterone ee 0.1 ml saliida 4 h ka hor imtixaanka. Dhammaan nidaamyada waxaa ansixiyay Guddiga Daryeelka Xoolaha ee Jaamacadda Western Ontario iyo waafaqsan tilmaamaha ay soo saartay Golaha Kanada ee Xannaanada Xoolaha.

Naqshad Sameynta

Tijaabooyinka 1 iyo 2: Jiirka (n = 37) ayaa loo oggolaaday in ay la galmoodaan haween qandaraaska ah (E) ama 30 min, kuwaas oo marki hore ugu yimid cilad baadhitaan nadiif ah (60 × 45 × 50 cm) mudo shan sano ah -waxbarashada isku dhafka hore ee imtixaanka, si loo helo khibrad jinsi. Intii lagu jiray labadii kulan ee ugu dambeeyay, dhammaanba xuduudaha istaandarka ah ee lagu sameeyay galmoodka ayaa la duubay, oo ay ka mid yihiin: Muuqaalka buurta (ML), waqtiga laga bilaabo haweenka ilaa koowaad (first mount), latency intrusion (IL: wakhtiga laga bilaabo haweenka ilaa daarta kowaad (marka laga reebo galmada ugu horreysa), marxaladda dheellitir la'aanta (PEI; waqtiga laga bilaabo ejaculation ilaa horraantii isdaba-joog), tirada boqollaal (M), iyo tirada isdhexgalka (IM)Agmo, 1997). Dhammaan ragga waxaa la siiyay 1 ml / kg maalin kasta oo 0.9% NaCl (saline); 3 maalmo isku xigta ka hor maalinta imtixaanka, habeynta habka loo xakameeyo iyo duritaanka. Maalin maalmaha ka horraysa maalinta imtixaanka, dhammaan ragga ayaa hal meel ku wada degan. Ragga qibrada leh, Fos-ka waxaa lagu soo bandhigi karaa calaamado xaddidan oo la xidhiidha waayo-aragnimada jinsiga hore (Balfour et al, 2004). Sidaa daraadeed, dhammaan isku dhafka iyo maareynta xakamaynta inta lagu guda jiro imtixaanada ugu dambeeya waxaa lagu qabtey qafiska guriga (iska ilaalinta calaamadaha la saadaaliyay) si looga hortago dhaqdhaqaaqa xaalad-celin ee ragga aan xakamayn. Ragga waxaa loo qaybiyey siddeed kooxood oo tijaabo ah oo aan kala duwaneyn waxqabadka galmada inta lagu jiro labadii kulan ee ugu dambeeya ee la isku daray (macluumaadka aan la muujin). Inta lagu jiro tijaabada ugu dambeysa, raga waxaa loo ogolaaday in ay ku duubaan qafisashadooda guriga illaa ay soo bandhigaan jahawareer (jinsi) ama aysan helin lamaane haween ah (galmo). Dhammaan ragga labka ah waxay ahaayeen kuwo daqiiqado 60 dhamaystiray kadib markii bilawga laysku daro si ay u oggolaadaan falanqaynta falsafada laysku daro. Dumarka waxaa la siiyay cirbadeynta 4 mg / kg Meth ama 1 ml / kg saline (sc) (n = 4 kasta), 10 (tijaabin 1) ama 15 (tijaabin 2) ka hor inta aanad kicin, si loo baaro fosforye MAP kinase. Qiyaasta iyo wakhtiga ka hor dhererka waxay ku saleysantahay warbixinnadii hore (Choe et al., 2002, Choe iyo Wang, 2002, Chen iyo Chen, 2004, Mizoguchi iyo al., 2004, Ishikawa et al., 2006). Kooxaha kantaroolka ah waxay ku jiraan ragga aan ku duugin, laakiin waxay heleen Meth 10 (n = 7) ama 15 (n = 5) ka hor intaan la bixin ficil, ama salineedyo 10 (n = 5) ama 15 (n = 4) ka hor intaan la bixin . Ka dib bixinta, maskaxda waxaa lagu baaraandegay immunohistochemistry.

Tijaabo 3: maaddaama dose sare loo isticmaalo Meth loo isticmaalo tijaabada 1 iyo 2, tijaabo dheeri ah oo dheeri ah ayaa loo sameeyaa si loo baaro haddii dabeecadaha galmada iyo qadar yar oo Meth ah ay ku dheehan tahay qiyaasta daaweyn ku salaysan xakamaynta neerfaha. Daraasadan waxaa lagu sameeyay hab isku mid ah tijaabooyin 1 iyo 2. Hase yeeshee, imtixaanka ugu dambeeya, kooxaha la isku daray iyo kuwa aan la isku halleynin (n = 6 kasta) waxay heshay 1 mg / kg Meth (sc) 15 ka hor intaan la bixin.

Tijaabinta 4: Si loo baaro haddii uur-ku-dareen-celinta ay sababto jinsiga iyo Meth uu yahay mid gaar ah Meth, tijaabadan waxaa lagu baarayaa haddii qaababka isku midka ah ee isku-dhafka neef-qabadka ee lagu arko d-amphetamine (Amph). Tijaabadan waxaa lagu sameeyay hab isku mid ah tijaabooyin 1 iyo 2. Si kastaba ha ahaatee, imtixaanka ugu dambeeya, ragga waxaa loo maamulay amph (5 mg / kg) ama saline (1 mg / kg) (sc) 15 ka hor intaan la bixin (n = 5 kasta). Xakamaynta ragga raga aan la aqoon waxay heleen cusbada ama daqiiqadaha Amph 15 ka hor intaan la bixin. Faahfaahin guud ee kooxda tijaabada ah ee loo isticmaalay tijaabooyinka 1-4 ayaa la bixiyaa Shaxda 1.

Shaxda 1       

Guudmarka kooxaha tijaabada ah waxaa ku jira tijaabooyinka 1-4.

Diyaarinta Cadka

Xayawaanka ayaa lagu suuxiyay pentobarbital (270 mg / kg; ip) iyo udubdhexaad ahaan 5 ml salineed kadibna 500 ml 4% paraformaldehyde ee 0.1 M phosphate buffer (PB). Mucaaradka ayaa la saarey kadibna dib loo dhigey 1 h heerkulka qolka isla xajmiga, ka dibna wuxuu ku dhuftay 20% sukrose iyo 0.01% Sodium Aziide ee 0.1 M PB waxaana lagu kaydiyaa 4 ° C. Qeybta Coronal (35 μm) ayaa lagu jaray mikrotome (H400R, Micron, Jarmalka), oo lagu soo ururiyey afar taxane ah oo isku mid ah oo loo yaqaan 'cryoprotectant solution' (30% sukrose iyo 30% ethylene glycol in 0.1 M PB) oo lagu kaydiyey 20 ° C ilaa shaqeynta.

Immunohistochemistry

Dhammaan kulubka waxaa lagu sameeyey heerkulka qolka oo ay ku dheelitiranyihiin. Qeybaha bilaashka ah ee la nadiifiyey waxaa lagu dhaqay si aad u badan oo leh 0.1 M Phosphate-tampered saline (PBS) inta udhaxeysa. Qaybaha waxaa lagu kululeeyay 1% H2O2 10 min, ka dibna la xakameynayo xalka kulaylka (PBS oo ka kooban 0.1% serum albumin ah iyo 0.4% Triton X-100) ee 1 h.

PERK / Fos

Tissue ayaa la iskula kulmay habka daawada polyclonal ee bakteeriyada ee P42 iyo p44 oo laga soo xigtay ERK1 iyo ERK2 (PERK; 1: 400 tijaabin 1 badan 19; 1: 4.000 2 3 iyo 21 badan 9101; Muuqaalka Calaamadaha Kumbuyuutarka # 1; 1 h laguna naqshadeeyay dameerka dufanka lafdhabarta ee IgG (500: 1; Sheybaarka Jarmal Immunoresearch Laboratories, West Grove, PA) iyo kakoobka avidin-horseradish peroxidase (ABC Elite; 1000: 10; Shaybaarada Wareega, Burlingame, CA). Kadibna, nudaha ayaa lagu kululeeyay 1 min oo leh tyramid biyotinylated biotinylated (BT; 250: 0.003 ee PBS + XNUMX% H2O2; Tennamid Signal Amplification Kit, NEN Life Sciences, Boston, MA) iyo for 30 min oo leh Alexa 488 oo lagu soo koobay strepavidin (1; Xermo Immunoresearch Laboratories, West Grove, PA). Dukumiinti waxay kuxirantahay habka loo yaqaan 'c-Fos' (100: 1; SC-500; Santa Cruz Biotechnology, Santa Cruz, CA), oo ay ku xigto 52 min minucub iyada oo la marin-habaabiyo anti-rabbi Alexa 30 (555: 1, Sheybaarka Jackson Immunoresearch Laboratories, West Grove, PA). Ka dib markii la xoqay, qaybaha waxaa lagu dhaqay si buuxda 200 M PB, oo lagu rakibay galabyada dhalada leh 0.1% jelatin ee ddH20 oo lagu daboolay dhexdhexaad dhexdhexaad ah (Gelvatol) oo ka kooban wakiil ka hortagaya anti-fading 1,4-diazabicyclo (2,2) octane (DABCO; 50 mg / ml, Sigma-Aldrich, St. Louis, MO). Xakamaynta Immunohistochemical waxaa ka mid ah ka takhaluska labada ama labada jeermis ee asaasiga ah, taas oo keentay maqnaansho calaamadeyn ah oo ku xiran mawjada ku habboon.

Falanqaynta Xogta

Dabeecadaha galmada

Dhammaan afartii tijaabo, xuduudaha istaandarada ee waxqabadka jinsiga ayaa la duubay sida kor lagu sharxay loona falanqeeyay iyadoo la adeegsanayo falanqayn kala duwanaansho (ANOVA). Falanqaynta xogta ee habdhaqanka galmada inta lagu jiro maalinta ugu dambeysa ee imtixaanka ayaa muujinaysa farqi weyn oo u dhexeeya kooxaha mid kasta oo ka mid ah xuduudaha waxqabadka galmada.

PERK / Fos-naatiijada Unugyada

Unugyada hal mar iyo labadaba ee loogu talagalay Fos iyo pERK ayaa lagu tiriyey heerarka qiyamka ee NAc-yada iyo qaybaha hoose, amygdala-ga baska ah (BLA), amygdala medial amygdala (MEApd), amygdala dhexe (CeA), nukleel medial preoptic (MPN), posteromedial iyo guska sariirta ee posterolateral of terminal terminal (BNSTpm iyo BNSTpl), iyo aagga barafka hore (ACA), prelimbic (PL), iyo infralimbic (IL) hoosaadyada mPFC. Sawirada waxaa lagu qabtay kamarad CCD oo la qaboojiyey (Microfire, Optronics) oo ku xiran Leica Microscope (DM500B, Leica Microsystems, Wetzlar, Jarmalka) iyo software Neurolucida (MicroBrightfield Inc) oo leh goobo kamarad xaddidan oo loogu talagalay dhammaan maadooyinka (iyadoo la adeegsanayo ujeedooyinka 10x). Isticmaalka nuurolucucida software, goobaha falanqaynta ayaa lagu qeexay saldhigyada (Swanson, 1998) u gaar ah gobol kasta maskaxda (eeg Jaantuska 1). Meelaha caadiga ah ee falanqaynta ayaa lagu isticmaalay dhammaan meelaha marka laga reebo asaasiga NAc iyo qolofka. Meelaha ugu dambeeya, FERO iyo Fos-u-bandhigiddu ma aha mid isku mid ah oo u muuqday qaabab yaryar oo la mid ah. Sidaa daraadeed, dhammaan asaasiga iyo qolofka waxa lagu sharaxay iyadoo lagu saleynayo calaamadaha (gawaarida dhinaca dambe, dhinaca madadaalada, jasiiradaha Calleja). Meelaha falanqaynta looma kala duwanaayo kooxaha tijaabada ah, waxayna ahaayeen 1.3 mm2 gudaha NAc core iyo qolof. Meelaha caadiga ah ee falanqaynta meelaha haray waxay ahaayeen: 1.6 mm2 gudaha BLA, 2.5 iyo 2.25 mm2 ee MEApd iyo CeA siday u kala horreeyaan, 1.0 mm2 MPN, 1.25 mm2 ee BNST iyo qaybaha mPFC, iyo 3.15 mm2 ee VTA. Laba qaybood ayaa loo kala soocay labada dhinac ee maskax kasta oo xayawaan ah, iyo tiro unugyo hal iyo labo ah oo loogu talagalay PERK iyo Fos iyo sidoo kale boqolleyda unugyada PERK ee muujiyay calaamad Fos. Dhibaatooyinka 1, 2, iyo 4, celceliska kooxaha ayaa la barbardhigey iyadoo la isticmaalayo laba hab oo ANOVA ah (qodobbada: isku dhafka iyo daroogada) iyo Fisher LSD hose ah isbarbardhigga heer muhiim ah ee 0.05. Imtixaanka 3, celceliska kooxaha ayaa la barbardhigey iyadoo la adeegsanayo imtixaannada aan tayada lahayn ee imtixaanka ee heerka xajmiga ee 0.05.

Jaantuska 1       

Jaantusyada muuqaalka iyo sawirrada muujinaya meelaha maskaxda ee falanqaynta. Goobaha falanqaynta ee lagu muujiyay waxay ku saleysan yihiin calaamadaha caanka ah ee gobol kasta oo maskaxda ah, ma aysan kala duwaneyn kooxaha udhaxeeya, waxayna ahaayeen 1.25 mm2 qaybaha mPFC (a), 1.3 mm2 ee ...

sawirka

Sawirro digital ah Jaantuska 3 waxaa lagu qabtay iyadoo la isticmaalayo kamarad CCD (DFC 340FX, Leica) oo ku xiran Leica microscope (DM500B) waxaana lagu soo geliyey Adobe Photoshop 9.0 (Adobe Systems, San Jose, CA). Sawirada laguma bedelin qaab kasta marka laga reebo qaabeynta iftiinka.

Jaantuska 3       

Sawirada wakiilada ee qaybaha NAc-ga ee loo yaqaan 'Fos' (red, a, d, g, j) iyo pERK (cagaar, b, e, h, k) ee xayawaanka koox kasta oo tijaabo ah: Isma galmo + Sal (a, b, c) , Galmada + Sal (d, e, f), Looma galmoodin + Meth (g, h, i), iyo Galmada + Meth (j, k, l). Xayndaabka midig waa ...

Natiijooyinka

Dhaqdhaqaaqa Nuclearka ee Nidaamka Xaddidaadda ee Dhaqanka Galmada iyo Maamulka Meth

Tijaabinta 1: Falanqeynta unugyo hal iyo labeeyn leh oo loogu talagalay Fos iyo Meth-ku-dhajiyey PERK ragga oo helay meth 10 daqiiqo kahor ficil-qaadis faahfaahsan oo ku saabsan Fos mooye-ku-ool ah ee MPN, BNSTpm, NAc core iyo shell, BLA, VTA, iyo qaybaha kala duwan ee mPFC, oo waafaqsan daraasado hore oo muujinaya falsafada Fosiga ah ee mawduucyada ah (Baum iyo Everitt, 1992, Pfausus iyo Heeb, 1997, Veening iyo Coolen, 1998, Hull et al., 1999). Maamulka Meth 10 daqiiqo kahor bixinta PERK ee NAc asaasiga ah iyo qolof, BLA, MeApd, CeA, BNSTpl, iyo gobollada mPFC, oo waafaqsan nidaamyada firfircoon ee ay sababeen nafsiyaadka kale ee nafsiga ah (Valjent et al., 2000, Valjent et al., 2004, Valjent et al., 2005).

Waxaa intaa dheer, seddex qaab oo iskudhaf ah oo ku saabsan dhaqdhaqaaqa neerfaha by habdhaqanka galmada iyo Meth ayaa lagu arkay: Marka hore, meelaha maskaxda lagu aqoonsaday meesha jinsiga iyo daroogada ay u hawlgalaan dadka dareen la'aanta ah (Shaxda 2). Gaar ahaan, CeA, MEApd, BNSTpl, iyo mPFC, koror weyn ayaa ku yimid labadaba daroogada ay keento PERK (F (1,16) = 7.39-48.8; p = 0.015- <0.001) iyo Fos-kufsi jinsiyeed (F (1,16, 16.53) = 158.83-0.001; p <1,16) ayaa la arkay. Si kastaba ha noqotee, gobolladan ma jirin wax kor u kac weyn oo ku yimid labada dareemayaal calaamadeysan ee ragga la daweeyey Meth. Kaliya marka laga reebo waxay ahayd MEApd, halkaas oo saameyn ku yeelatay lambarada tirooyinka unugyada laba-calaamadeysan la helay (F (9.991) = 0.006; p = XNUMX). Si kastaba ha noqotee, ma jirin wax saameyn ah oo guud oo daaweynta daroogada ah iyo calaamadeynta labada koox ee Meth lagu daweynayay si aad ah ugama sarreeynin kooxaha cusbada lagu daaweeyo, sidaas darteed ma uusan keenin daroogada (Shaxda 2). Marka labaad, meelaha maskaxda ayaa la ogaadey meesha dhaqdhaqaaqa neuraliyadu ay sababtay macaamil (Shaxda 3). Gaar ahaan, MPN, BNSTpm, iyo VTA waxaa lagu dhaqaajiyey oo keliya mareeyaha, waxaana ku jira kororka muuqda ee Fos (Foomka) (X (1,16) = 14.99-248.99; p ≤ 0.001), laakiin ma laha MER-PERK.

Shaxda 2       

Faahfaahinta qiyaasta Fos iyo Meth-ku-dhalis-darrada ah ee maskaxda ee meelaha maskaxda ah ee jinsiga iyo daroogada ay u dhaqmaan dadka dareenka ah ee aan ciriiri ahayn.
Shaxda 3       

Faahfaahinta foornada Fos iyo Meth-ku-dhalis-darrada ah ee maskaxda maskaxda ah halkaasoo dhaqdhaqaaqa neuraliyu ay sababtay kaliya maadada.

Ugu dambeyntii, goobaha maskaxda waxaa laga helay meesha galmoodka iyo daroogada ay dhaqdhaqaaqa ku kaceen dad badan oo ka soo jeeda qanjirrada (Jaantuska 2 iyo Iyo 3) .3). Marka la eego NAc core iyo shell, BLA, iyo ACA, waxaa jiray saameyn guud oo ku saabsan isku dhafka (F (1,16) = 7.87-48.43; p = 0.013- <0.001) iyo daaweynta daroogada (F (1,16) = 6.39– 52.68; p = 0.022- <0.001), iyo sidoo kale isdhexgalka ka dhexeeya labadan arrimood (F (1,16) = 5.082-47.27; p = 0.04- <0.001; isdhexgal la taaban karo malaha ACA) tirada unugyada muujiya labadaba mataano-ku-kicisay Fos iyo MET-ku-kallifaad Falanqaynta 'post hoc analysis' ayaa muujisay in lambarrada dareemayaasha laba-cirifoodka ah ay si aad ah uga sarreeyaan ragga la isku duro ee Meth-ka la barbardhigo Meth-ku-daweynta aan fiicnayn (p = 0.027- <0.001), ama cusbada la daweeyay (p = 0.001- <0.001) ragga (Jaantuska 2 iyo Iyo 3) .3). Marka xogta lagu soo bandhigay boqolleyda nuucyada dawada ee daroogada, 39.2 ± 5.3% ee xudunta NAc, 39.2 ± 5.8% ee NAc qolof, 40.9 ± 6.3% ee BLA, iyo 50.0 ± 5.3% ACA qanjirka labaduba waxay ahaayeen lab iyo dhedig.

Jaantuska 2       

Foornada Fosiga iyo Meth-ku-xigeenka ee NAc, BLA, iyo ACA dareemayaasha 10 min ka dib markii la maamulo 4 mg / kg Meth. Tirooyinka celceliska ah ee naqshadeynta caanaha NAc (a, d, g, j), pERK (b, e, h, k), iyo laba (c, f, i, l) ...

Kormeer aan la fileyn ayaa ah in dabeecadda galmada ay saameysay PER-PERK. Inkasta oo Meth ay si weyn u sababtay heerarka PERK ee labadaba meth-laysku dardarey, kooxaha NAc, BLA, iyo ACA, calaamadeyntu waxay si aad ah hoos ugu dhigtay ragga meth-ku-fool leh marka la barbardhigo ragga meth-ku-fool ah (Jaantus 2b, e, h, k; p = 0.017- <0.001). Natiijadani waxay sii wadi kartaa taageerada ah in jinsiga iyo daroogadu ay u dhaqmaan isla muruqyada isku midka ah, laakiin waxa kale oo laga yaabaa inay muujinayso isbeddelka is-beddelka ee daaweynta daroogada ama metabolism-ka taas oo keenta in ay beddesho jawaabaha neeriga ah ee Meth. Si loo baaro haddii dabeecadaha galmada ay keenaan qaab kale oo ku-meel-gaadh ah oo ah hawl-galinta daroogada sababtay, qaybaha NAc, BLA, iyo ACA ayaa loo musuqay ragga raga oo la siiyay waqti dambe (15 min) ka dib markii maamulka daroogada (tijaabi 2).

Tijaabinta 2: Falanqeynta unugyada hal mar iyo labadaba waxay xaqiijiyeen natiijooyinka kor lagu sharaxay habdhaqanka jinsiga iyo marxaladaha dambe ee Meth 15 kahor ficilka ka dib waxay keentay koror ballaaran oo Fos iyo PERK immunolabeling ee NAc core iyo shell, BLA, iyo ACA. Waxaa intaa dheer, isbarbar dhaf ah oo muujinaya foornada Fos iyo Meth-induced PERK ayaa mar kale laga helay meelahaas (Jaantuska 4; Saamaynta galmada: F (1,12) = 15.93-76.62; p = 0.002- <0.001; saameynta daroogada: F (1,12) = 14.11-54.41; p = 0.003- <0.001). Tirada labada dareemayaal calaamadeysan ee labka ah ee la isku duro Meth-ka ayaa si aad ah uga sarreeyay marka la barbardhigo Meth-da aan la daaweynin (p <0.001) ama cusbada lagu daaweeyay (p <0.001) ragga Markii xogta lagu muujiyay boqolleyda neerfayaasha firfircoon ee daroogada shaqeeya, 47.2 ± 5.4% (NAc core), 42.7 ± 7.6% (NAc shell), 36.7 ± 3.7% (BLA), iyo 59.5 ± 5.1% (ACA) ee neerfayaasha firfircoon. by mating waxaa sidoo kale hawlgeliyay Meth. Intaa waxaa sii dheer, KHARASHKA daroogada ay ku kala duwanaan waayeen xayawaanka la daaqay iyo kuwa aan duugoobin (Jaantus 4b, e, h, k), dhammaan aagagga marka laga reebo ACA (p <0.001). Xogtaani waxay muujineysaa in dabeecadaha galmada ay dhab ahaantii sababaan wax ka beddelka qaabka ku-meelgaarka ah ee PERK induction ee Meth.

Jaantuska 4       

Foornada Fosiga iyo Meth-ku-xigeenka ee NAc, BLA, iyo ACA dareemayaasha 15 min ka dib markii la maamulo 4 mg / kg Meth. Tirooyinka celceliska ah ee naqshadeynta caanaha NAc (a, d, g, j), pERK (b, e, h, k), iyo laba (c, f, i, l) ...

Dhaqdhaqaaqa Nuugyada Ka Hortagga Dhaqanka Galmada iyo 1 mg / kg Meth

Natiijada fog waxay muujisay in dabeecada galmada iyo 4 mg / kg Meth ay ku fashilmeen dad badan oo ka dhexjirta nuuroonta NAc iyo shell, BLA, iyo ACA. To Baaritaan ku sameynta saameynta daroogooyinka-qiyaasta isku-dhafan ee ku-meel-gaadhka ah, qaababka hawl-galinta neerfurka ayaa sidoo kale la baray iyadoo la isticmaalayo qadar yar oo ah Meth. NAc core iyo shell, BLA, iyo ACA ayaa lagu falanqeeyey waxqabadka ay ku kacday galmada iyo Meth. Xaqiiqdii, habdhaqanka galmada iyo soo-gelinta dambe ee Meth waxay keentay in korodhka weyn ee Fos iyo PERK immunolabeling ee qaybaha NAc iyo hoose ee BLA, iyo sidoo kale neurons ee gobolka ACA ee mPFC (Jaantuska 5). Qeybta hoose ee Meth ayaa keentay in tiro yar oo ah nooca "PERK" lagu calaamadiyay nuucyada astaamaha ah ee 4 mg / kg Meth ee afarta maskaxda ee la falanqeeyay. Muhiimadda ugu muhiimsan, NAc core iyo shell, BLA, iyo ACA waxay muujiyeen korodh weyn oo ah tirada unugyada labka ah ee la calaamadiyay (Jaantus 5c, f, i, l) marka la barbardhigo ragga aan la taaban ee Meth-duriyey (p = 0.003- <0.001). Markii xogta lagu muujiyay boqolleyda neerfayaasha firfircoon ee daroogada shaqeeya, 21.1 ± 0.9% iyo 20.4 ± 1.8% ee NAc core iyo shell siday u kala horreeyaan, 41.9 ± 3.9% ee BLA, iyo 49.8 ± 0.8% ee ACA dareemayaasha waxaa lagu dhaqaajiyey jinsi iyo Meth.

Jaantuska 5       

Foornada Fosiga iyo Meth-ku-xigeenka ee NAc, BLA, iyo ACA dareemayaasha 15 min ka dib markii la maamulo 1 mg / kg Meth. Tirooyinka celceliska ah ee naqshadeynta caanaha NAc (a, d, g, j), pERK (b, e, h, k), iyo laba (c, f, i, l) ...

Dhaqdhaqaaqa neuraliska ka dib dhaqan galmoodka iyo maamulka d-Amphetamine

Si loo tijaabiyo in natiijooyinka kor ku xusan ay yihiin meth u gaar ah, tijaabo dheeri ah ayaa loo sameeyey si loo barto mate- iyo Amph-ku-dallacsiinta maskaxda. Falanqaynta unugyada hal mar iyo labadaba loogu talagalay PERK iyo Fos waxay muujiyeen in habdhaqanka galmada iyo ku-soo-dhowaanshaha Amph inay sababtay koror ballaaran oo Fos iyo PERK immunolabeling ee NAc core iyo qolof iyo BLA (Jaantuska 6; Saamaynta galmada: F (1,15) = 7.38-69.71; p = 0.016- <0.001; saameynta daroogada: F (1,15) = 4.70-46.01; p = 0.047- <0.001). Intaa waxaa sii dheer, tirooyinka dareemayaasha laba-geesoodka ah ayaa si aad ah uga sarreeya Amph-da lagu daweynayo marka la barbar dhigo Amph-la daaweyn (p = 0.009- <0.001), ama cusbada la daweeyay (p = 0.015- <0.001) ragga (Jaantus 6c, f, i). Marka xogta loo soo bandhigay boqolleyda nuucyada dawada ee daroogada, 25.7 ± 2.8% iyo 18.0 ± 3.2% ee NAc core iyo shellada siday u kala horreeyaan, iyo 31.4 ± 2.0% Xayawaanka BLA waxaa loo isticmaalay labadaba labiska iyo Amph. Gobolka ACA ee mPFC waxay soo bandhigeen heerar aad u sarreeyaJaantus 6j; F (1,15) = 168.51; p <0.001). Si kastaba ha noqotee, si ka duwan Meth, Amph ma uusan keenin koror weyn oo ku yimaada heerarka daroogada ee daroogada ee ACA (Jaantus 6k) ama tirada nairon-ka labajibaaray ee labadaba ACA (Jaantus 6l) marka la barbardhigo labadaba labka dheddig-lab ah oo aan la jarjarin oo aan la jarin.

Jaantuska 6       

Foosto iyo Fahfadhiyo Caanood oo lagu magacaabo NAc, BLA, iyo ACA neurons 15 min ka dib markii la maamulo 5 mg / kg Amph. Tirooyinka celceliska ah ee naqshadeynta caanaha NAc (a, d, g, j), pERK (b, e, h, k), iyo laba (c, f, i, l) ...

DHIBAATOOYINKA

Daraasadani waxay muujineysaa heerarka gacanta oo isku dhafan oo u dhexeeya naqshadaha neerfaha ee dabiiciga ah ee dabeecada galmada iyo meth. Sidaa daraadeed, xogtaasi waxay muujinayaan in uunan daroogo ku dhaqmin isla gobolada maskaxda ee nidaaminta abaalmarinta dabiiciga ah, laakiin dhab ahaantii, daroogooyinka waxay u hawlgalaan unugyo isku mid ah oo ku lug leh xeerka dabiiciga ah. Gaar ahaan, waxaa halkan lagu muujiyay in habdhaqanka galmada iyo Meth ay si wada jir ah u-hawlgalaan dadweynaha qanjidhada NAc iyo xayawaanka, BLA, iyo ACA ee mPFC, aqoonsashada goobaha laga yaabo inay Meth saameyn ku yeelan karto dhaqanka galmada.

Natiijada hadda ee ah habdhaqanka galmada iyo maamulka Meth ayaa u hawlgalaya dadka ka soo horjeeda qanjirrada NAc, BLA, iyo ACA inay ka duwan tahay natiijooyinka ka soo baxa daraasado kale oo muujinaya in dadyowga kala duwan ee NAc neurons ay ku qortaan daroogada iyo abaalmarinta dabiiciga ah.

Gaar ahaan, daraasadaha electrophysiological ee marka la barbardhigo dhaqdhaqaaqa neuraliyowga inta lagu jiro is-maamulidda abaal-marin dabiiciga ah (cunto iyo biyo) iyo kookeynta xididada dhiigga ayaa muujiyay in isku-dhafka kookeeynta uu kiciyay dadweyne kala duwan, oo aan dadku ka badnayn nuuroonyada oo guud ahaan aan wax jawaab ah u lahayn inta uu shaqeynayay biyaha iyo xoojinta cuntada (92%). Kaliya 8 boqolkiiba qanjidhada ciriiriga ayaa muujiyay in ay dhaqdhaqaaq u leeyihiin kocainka iyo abaalmarinta dabiiciga ah labadaba (Carelli iyo al., 2000).

Taa ka soo horjeeda, aqlabiyadda (65%) ee unugta NAc waxay muujisay in ay dhaqdhaqaaqyo kala duwan ay sameeyeen (cunto iyo biyo), xitaa haddii mid ka mid ah xoojiyay uu ahaa mid la mid ah (sukrose) (Roop et al., 2002).

Waxyaabo dhowr ah ayaa laga yaabaa in ay ka qaybqaataan isbarbar dhigga natiijooyinka iminka jira. Marka hore, habab farsamo oo kala duwan ayaa loo isticmaalay in lagu baaro dhaqdhaqaaqa neuraliska. Daraasaddan hadda la adeegsaday habka neuroanatomiga ee lagu ogaanayo isku-socodka nukliyeerka ee laba jeer oo kala duwan iyadoo la adeegsanayo ficil-maskaxeed shucaac ah oo loo yaqaan Fos iyo PERK, taas oo u oggolaaneysa baaritaanka hal unug firfircoon oo unugyada maskaxda ah. Taa ka soo horjeeda, daraasaadka ay sameeyeen Carelli iyo shaqaalaha la shaqeeya waxay isticmaalaan diiwaanka farsamada gacanta oo lagu xaddiday NAc ee dhaqanka xayawaanka si ay wax uga qabtaan haddii is-maamulidda daroogada xadgudubka ay u dhaqaajiso wareegga isku-midka ah ee loo isticmaalo abaalmarinta dabiiciga ah.

Marka labaad, daraasaddan hadda baaray abaalmarin dabiiciga ah oo kala duwan, sida dhaqanka galmada marka la barbar dhigo daraasadihii hore, oo isticmaalay cunto iyo biyo jaad ah (Carelli, 2000). Cuntada iyo biyaha waxay yeelan karaan qiime ka yar qiimaha ka yar inta laysku daro. Habdhaqanka galmada waa mid si fiican u abaalmarin lehna jiirka si fudud ayaa loo dhisi karaa CPP si loo naaquso (Agmo iyo Berenfeld, 1990, Martinez iyo Paredes, 2001, Tenk, 2008). Inkasta, jiirka cunnooyinka xadidan waxay sameysaan CPP biyo (Agmo et al., 1993, Perks iyo Clifton, 1997) iyo cunto (Perks iyo Clifton, 1997), djet jadwalka aan xadidneyn waxay doorbidaan oo sameeyaan CPP raashin badan oo la kariyey (Jarosz et al., 2006, Jarosz et al., 2007).

Saddexaad, waxbarashadayadu waxay ku jiraan daroogooyinka kala duwan ee xadgudubka marka la barbar dhigo daraasadihii hore, iyagoo isticmaalaya methamphetamine iyo amphetamine halkii kokainiga. Natiijooyinka iminka socda ayaa muujinaya in gaar ahaan Meth, iyo heerkul yaraanta amphetamine, ay sababtay in la kiciyo nuuroonnada ay sidoo kale dhaqdhaqaaqa galmo sameeyaan. Waayo-aragnimada daroogada ayaa sidoo kale laga yaabaa inay sidoo kale isbedeshay natiijooyinkayaga. Daraasaddan iminka waxay isticmaashay xayawaan lagu sameeyay galmo, laakiin daroogada maandooriyaha. Taa bedelkeeda, daraasaadka korontada ku shaqeeya ee Carelli iyo shaqaalahoodu waxay isticmaalaan xayawaanno "si fiican loo tababaray" kuwaas oo heley soo noqnoqoshadooda kookeynta.

Sidaa awgeed, waxaa suurtagal ah in meth-ku-dallacsiinta firfircoonaanta nuuroon ee dhaqdhaqaaqa galmoodka lagu bedelay jiirka jariimooyinka khibrad u leh. Si kastaba ha ahaatee, daraasad horudhac ah oo ka timid shaybaarkeenna ayaa soo jeedinaysa in khibradda maandooriyaha aan loo baahnayn in ay noqoto mid muhiim u ah habdhaqanka galmada iyo daawaynta Meth ee ragga si joogto ah loogu daaweeyo Meth oo la mid ah boqolleyda isla'egyadan ee ku dhaca nuuroonada sida lagu sheegay daraasadda hadda (20.3 ± 2.5% ee NAc core iyo 27.8 ± 1.3% ee NAc ee qolka NAc; Frohmader iyo Coolen, aragti aan la daabicin).

Ugu dambeyntii, daraasaddan hadda baaray "tallaabada tooska ah" ee daroogada isticmaalka maamulka baaskiilka. Sidaa daraadeed, falanqaynta iminka ma muujinayso macluumaadka ku saabsan wareegyada neerfaha ee ku lug leh raadinta daroogada ama calaamadaha la xidhiidha abaalmarinta daroogada, laakiin waxay muujinaysaa dhaqdhaqaaqa neerfaha ee ay keentay ficilada daawada ee daroogada. Daraasadihii hore ee farsamada cilmi-baarista, NAc dhaqdhaqaaqa neuralada ee dhacaya mudo gudahood jawaabaha xoogga leh maaha natiijada farqiga daaweynta ee kookeynta, laakiin waxay si weyn ugu tiirsan tahay arrimaha ku lug leh is-miidaaminta is-maamulka (Carelli, 2000, Carelli, 2002). Gaar ahaan, waxqabadka NAc wuxuu saameyn ku yeeshaa soo-jeedinta madax-bannaan ee calaamadaha la xidhiidha keenista cocaine-ka iyo sidoo kale qalabka korantada (ie, lever pressing) taas oo ku jirta barxad this habdhaqanka ah (Carelli, 2000, Carelli iyo Ijames, 2001, Carelli, 2002, Carelli iyo Wightman, 2004). Soo koobid, natiijooyinka noocan ah ee wadashaqeynta ee abaalmarinta dabiiciga ah iyo daroogada waxay noqon kartaa mid gaar ah oo loogu talagalay dhaqdhaqaaqa galmoodka oo si haboon loo maamulo Meth iyo Amph.

Meth iyo jinsi-firfircooni firfircoon ee dadka neconka ah ee neur-malarka ee NAc-yada iyo qolofka habka ku-tiirsan. Neer-ka-naqshadeynta nuucyada ee NAc ayaa dhexdhexaadin kara saameynta ay yeelan karto Meth ee ku saabsan dhiirigelinta iyo hantida abaal-marinta dabeecadaha jinsiga ah sida dhibaatooyinka NAc-da ay carqaladeeyaan dabeecadaha galmada (Liu et al., 1998, Kippin et al., 2004). Intaa ka sokow, nuucyadaas waxaa laga yaabaa inay noqoto meel ay ku dheehan tahay saameynta daroogada ku-tiirsan ee ku saabsan maadada, maaddaama qiyaasta hoose ee Meth (1 mg / kg) ay hoos u dhigtay tirada unugyada labajibbaarida ee 50% marka la barbar dhigo qadarka sare ee Meth (4 mg / kg). Inkasta oo daraasadani aanay sheegin astaamaha kiimikada ee neur-mareenada la wadaago, baaritaanadii hore waxay muujiyeen in fal-galinta daroogada iyo Fos-soosaarida ee NAc ay ku xiran tahay labada dopamine (DA) iyo qabtayaasha glutamate (Valjent et al., 2000, Ferguson et al., 2003, Valjent et al., 2005, Sun et al., 2008). Inkastoo aysan caddeyn haddii dhaqdhaqaaqa neerfaha ee NAc ay ku tiirsan yihiin kuwan soo dhaweeyaha, tan ayaa lagu soo bandhigay gobollada kale ee maskaxda, gaar ahaan degaanka ka hortagga daawooyinka (Lumley iyo Hull, 1999, Dominguez et al., 2007). THooyo, Meth waxay ku dhaqmi kartaa qanjidhada sidoo kale waxay dhaqdhaqaajineysaa inta lagu jiro dhaqanka galmada iyada oo la adeegsanayo dopamine iyo glutamate reseptors. Doorka NAc glutamate ee dhaqanka galmada hadda ma cadda, laakiin waxaa si fiican loo ogaaday in DA uu ka ciyaarayo kaalin muhiim ah ee dhiirigelinta dabeecadaha galmada (Hull et al., 2002, Hull et al., 2004, Pfaus, 2009). Daraasadaha Microdialysis ayaa sheegay in ay kordheen NAc DA efflux inta lagu jiro xilliyada cunto yaryar iyo kuwa isboortiga ee habdhaqanka galmada (Fiorino iyo Phillips, 1999a, Lorrain et al., 1999) iyo mesolimbic DA efflux ayaa la xiriirta fududeynta bilaabida iyo dayactirka dhaqanka galmada (Pfaus iyo Everitt, 1995). Intaa waxa dheer, baadhitaanada DA ayaa waxay muujinayaan in DA-da dadka ka soo horjeeda ee NAc ay joojiyaan dabeecadaha galmada, iyada oo agonistu ay fududeynayso bilawga dhaqanka galmadar (Everitt et al., 1989, Pfausf iyo Phillips, 1989). Sidaa daraadeed, Meth waxaa laga yaabaa inay saameyn ku yeelato dhiirigelinta dabeecadaha galmada iyada oo la adeegsanayo waxqabadka DA.

Marka loo eego NAc, tirada unugyada labajibbaaran ee BLA iyo ACA ayaa weli ah kuwo aan isbeddelin iyada oo aan loo eegin qiyaasta Meth. BLA waxay muhiim u tahay barashada isku-dhafan ee kala duwan oo si xooggan ugu lug leh xoojinta xoojinta iyo abaalmarinta abaalmarinta inta lagu jiro qalabka wax ka qabashada (Everitt et al., 1999, Cardinal et al., 2002, Eeg, 2002). Maydhayaasha lakabyada leh ee BLA waxay muujinayaan cirridka yar yar ee culeyska cunnooyinka lehEveritt et al., 1989) ama xoojinta galmada (Everitt et al., 1989, Everitt, 1990). Taas bedelkeeda, maareeyntaas ma saameynayso wejiga qadada ah ee quudinta iyo dhaqanka galmada (Cardinal et al., 2002). BLA waxay sidoo kale ka ciyaareysaa kaalin muhiim ah oo ku saabsan xasuusta dareenka la xariira dareenka daroogada (Grace iyo Rosenkranz, 2002, Laviolette iyo Grace, 2006). Nabaro ama fayadhowrka daawooyinka ee BLA waxay xannibayaan iibsashada (Whitelaw et al., 1996) iyo muujinta (Grimm iyo Arag, 2000) dib-u-soo-celinta cocaine-xaaladeed, iyada oo aan saamaynaynin nidaamka maamulka daroogada. Intaas waxaa dheer, Amph ayaa si toos ah loogu siiyay natiijooyinka BLA ee daroogo xoog leh oo dib-u-soo-kabasho ah iyada oo ay joogaan amarrada xaaladdooda (Fiiri et al., 2003). Sidaa daraadeed, waxaa suurtagal ah in gudbinta DA-da ee sii kordheysa ee DA-da ee BLA ay keentay saliida xooggan ee xooggan iyo raadinta (Ledford et al., 2003) ee abaalmarinta jinsiga, taas oo gacan ka gaysata isdhaafsiga galmada la xoojiyey iyo rabitaanka ay soo gudbiyeen dadka ku xadgudbay Meth (Semple et al., 2002, Green iyo Ringis, 2006).

ACA-da, kicinta neerfaha ee neur-ku-socodka galmada ayaa ahaa qiyaasta-madaxbannaan oo gaar ah Meth, maadaama aan lagu arag Amph. Inkasta oo Meth iyo Amph ay leeyihiin qaabdhismeedyo dabiici ah oo farshaxan ah, Meth waa maskaxiyan awood leh oo ka badan Amph oo leh saameyn joogto ah (NIDA, 2006). Daraasooyin by Goodwin et al. waxay muujisay in Meth ay soo saartay DA dheeraad ah oo ka hortagtay DAAWEYNTA oo ka hortagaya xayiraadda degaanka ee degaanka laga isticmaalo oo ka shaqeeya NAc ka badan Amph. Tilmaamahani wuxuu gacan ka geysan karaa sifooyinka khaaska ah ee Meth marka loo eego Amph (Goodwin et al., 2009) iyo laga yaabee kala duwanaanshaha isdhexgalka neeriga ee lagu arkay labada dawo. Si kastaba ha noqotee, ma cadda in hannaanka natiijooyinka kala duwan ay u sabab tahay farqiga udhexeeya faraqa u dhexeeya mukhaadaraadka ama waxtarka awoodda leh ee la xiriira qiyaasaha loo adeegsado iyo baaritaan dheeraad ah ayaa loo baahan yahay.

Isku-dubarid la'aanta Meth iyo jinsiga laguma arag meel hoosaadyada kale ee mPFC (IL iyo PL). Marka la eego, ACA waxaa si baaxad leh loo bartaa iyadoo la adeegsanayo hawlo firfircoon, oo gacan ka geysanaya doorka ururada kobcintaEveritt et al., 1999, Eeg, 2002, Cardinal et al., 2003). Waxaa jira caddaymo ballaaran in mPFC ay ku lug leedahay daroogada xakamaynta iyo dib ugu noqoshada dabeecada daroogada raadinta iyo daroogada ee labada qof iyo jiirka (Grant et al., 1996, Childress et al., 1999, Capriles et al., 2003, McLaughlin iyo Arag, 2003, Shaham et al., 2003, Kalivas iyo Volkow, 2005). AnigaN, tan waxaa la soo jeediyay in mPFC-da ay sabab u tahay soo noqnoqashada soo noqnoqoshada daroogada xadgudubka waxay masuul ka noqon kartaa koontaroolidda hoos u dhigista iyo korodhka dabeecadaha lagu maareeyo daroogada sida korka lagu arkay (Jentsch iyo Taylor, 1999). Macluumaadkii ugu dambeeyay ee shaybaaradayada ayaa muujiyey in xanuunada mPFC ay keenayaan in ay sii wataan raadinta habdhaqanka galmada marka tani la xiriirto kicinta (Davis et al., 2003). Inkasta oo daraasadani aysan baadhin ACA, waxay taageertaa mala-awaalka mPFC (iyo ACA gaar ahaan) dhexdhexaadinaysa saameynta Meth ee luminta xakamaynta dabeecadaha galmada sida ay u sheegeen dadka ka soo horjeeda Meth (Salo et al., 2007).

Ugu dambeyntii, wadashaqayntan oo dhan waxay wada sameeyaan tallaabo muhiim ah oo muhiim ah oo ku saabsan sida loo fahmayo sida daroogada xadgudubku u dhaqmaan ee ku saabsan jidadka neerfiga ee caadi ahaan dhexdhexaadiya abaalmarinta dabiiciga ah. Intaa waxaa dheer, natiijooyinkani waxay muujinayaan in ay ka duwan tahay rumaysiga hadda ee ah in daroogada xadgudubku aysan ku dhaqmin unugyada isku midka ah ee nidaamka mesolimbicda ah sida abaalmarinta dabiiciga ah, Meth, iyo qiyaasta ka hooseeya Amph, waxay u hawlgelisaa unugyada isku midka ah habdhaqanka galmada. Taas bedelkeeda, dadyawga nukliyarka ah ee la wadaago ayaa saameyn ku yeelan kara raadinta abaal-gudda dabiiciga ah ka dib soo-saarkiisa. Ugu dambeyntii, natiijooyinka daraasaddaani waxay si weyn uga qayb qaadan kartaa fahamkayaga aasaas u ah maandooriyaha guud ahaan. Isbarbardhigga isbarbardhigyada iyo kala duwanaanshaha, iyo sidoo kale isbeddel ku yimaadda naqshadaha neerfurka ee nidaamka mesolimbic ee ka soo horjeeda dabeecadaha galmada iyo daroogada xadgudubka waxay horseedi kartaa faham wanaagsan oo ku saabsan isticmaalka maandooriyaha iyo isbeddelka la xidhiidha abaalmarinta dabiiciga ah.

Mahadnaq

Cilmi-baaristaan ​​waxaa taageeray deeqo ka timid Hay'adaha Caafimaadka Qaranka ee R01 DA014591 iyo Machadyada Kanada ee Cilmi-baarista Caafimaadka RN 014705 LMC.

ABBREVIATIONS

  • ABC
  • avidin-biotin-malleradish peroxidase
  • ACA
  • aagga qoryaha hore
  • Amph
  • d-amphetamine
  • BLA
  • amygdala baslin
  • BNSTpl
  • marinka danbe ee santuuqa sariirta ee terminaalka stria
  • BNSTpm
  • santuuqa sariirta ee posteromedial of terminal terminal
  • BT
  • tyramide biotinylated
  • CeA
  • amygdala
  • CPP
  • doorbidista booska
  • E
  • xayawaan
  • EL
  • xayiraad la'aan
  • IF
  • aagga infralimbic
  • IL
  • latency intramination
  • IM
  • ra'yiga
  • M
  • Buur
  • MAP Kinase
  • kiniin macaan oo maskaxda ku jirta
  • MEApd
  • amygdala dhexdhexaad ah
  • Meth
  • methamphetamine
  • ML
  • Dhaqdhaqaaqa
  • mPFC
  • Kortex doorbid ah
  • MPN
  • daaweynta nudleelka maqaarka
  • NAc
  • nucleus Accumens
  • PB
  • fosfatiga buundada
  • PBS
  • fosfat saline-ka loo yaqaan
  • PEI
  • Boos-u-deynta dhalmada kadib
  • FURAN
  • Xilliga MAP ee fosfatiga
  • PL
  • aagga prelimbic
  • VTA
  • aagga ventral tegmental

Qoraalada

Diidmada Daabacaha: Tani waa faylka PDF ee qoraallada aan la saadaalin Karin ee la aqbalay daabacaadda. Adeeg ahaan macaamiisheena waxaan siineynaa qoraalkan hore ee qoraal gacmeedka. Qoraalku wuxuu qaadan doonaa nuqulka, qeexidda, iyo dib-u-eegista caddaynta la soo gudbiyey ka hor inta aan lagu daabicin foomka ugu dambeeya ee la heli karo. Fadlan xusuuso in inta lagu jiro qaladaad habka wax soo saarka laga yaabo in la ogaado taas oo saameyn karta mawduuca, iyo dhammaan sharciyeynta sharciga ah ee khuseeya qoraalka.

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