Front Behav Neurosci. 2014 Feb 11; 8: 36. doi: 10.3389 / fnbeh.2014.00036. eCollection 2014.
Zack M1, Featherstone RE2, Mathewson S3, Fletcher PJ3.
aan la taaban karin
Qabatinka waxaa loo arkaa inuu yahay cudur maskaxda ah oo ka dhasha soo-gaadhis joogto ah ee daroogada. Nidaamyada xasaasiga ah ee maskaxda dopamine (DA) ayaa qeyb ahaan dhexdhexaadiya saameyntaas. Khamaarka jirrada (PG) waxaa loo arkaa inuu yahay balwad dhaqan. Sidaa darteed, PG waxaa sababi kara soo-gaadhis joogto ah ee khamaarka. Aqoonsiga dareenka khamaarka ee ay keento nidaamyada DA ayaa taageeraya suurtagalnimadaas. Abaalmarinada khamaarka waxay dhalisaa DA in la sii daayo. Mid ka mid ah dhacdooyinka ciyaarta mashiinka ciyaarta ayaa wareejinaya jawaabta DA ee ka timaadda abaalmarinta ilaa bilawga raadadka (isweydaarsiga qaababka) abaalmarinta, iyadoo la raacayo mabaadi'da barashada farqiga u-ku-meelgaarka ah. Markaa, dhiirrigelinta shuruudaha leh (CS) waxay door muhiim ah ka ciyaaraan jawaabaha khamaarka ee DA. Horudhaca, jawaab-celinta DA ee CS ayaa ugu xoog badan marka ay suuragalnimada abaalmarintu tahay 50%. Jadwalkaan gudiga ah CS wuxuu keenayaa abaalmarin abaal marin laakiin ma bixiyo macluumaad ku saabsan haddii ay ku dhici doonto maxkamad la soo saaray. Inta lagu jiro khamaarka, jadwalka 50% waa inuu cadeeyo ugu badnaan DA sii daayo. Tani waxay si dhow ugu habboon tahay abaalmarinta celcelis ahaan (46%) mashiinka booska ganacsiga. Sii-daynta DA waxay ku biirin kartaa dareenka, gaar ahaan amphetamine. Soo-gaadhista joogtada ah ee CS oo saadaalinaysa abaalmarinta 50% ee waqtiga ayaa u ekkaan kara saamayntaas. Waxaan ku tijaabinay mala-awaalkan seddex daraasadood oo lagu sameeyo jiirka. Xayawaanku waxay heleen 15 × 45-min oo ay u bandhigaan CS oo saadaaliyay abaalmarin ay la socdaan itimaalka '0', 25, 50, 75, ama 100%. CS wuxuu ahaa nal; Abaalgudku wuxuu ahaa 10% sucrose solution. Tababbarka ka dib, jiirku wuxuu helay nidaam dareen-celin ah oo ah shan qiyaasood oo gooni ah (1 mg / kg) ee d-amphetamine. Ugu dambeyntiina waxay heleen 0.5 ama 1 mg / kg amphetamine caqabad ka hor imtixaanka waxqabadka jimicsiga 90-min. Dhammaan sedexda daraasadood kooxda 50% waxay soo bandhigeen nashaad ka weyn kooxaha kale iyagoo ka jawaabaya labada qiyaasood ee loolan adag. Cabbirrada saamayntu waxay ahaayeen kuwo dhexdhexaad ah laakiin waa mid joogto ah, sida ka muuqata urur muhiim ah × darajo kooxeed (ϕ = 0.986, p = 0.025). Soo-gaadhista joogtada ah ee jadwalka-sida khamaarka ah ee abaalmarinta dhiirrigelinta saadaalinta ayaa kor u qaadi kara dareenka amphetamine-ka sida soo-gaadhista amphetamine lafteeda.
Hordhac
Qabatinka waxaa lagu gartaa inuu yahay cudur maskaxda ah oo sababa soo-gaadhista joogtada ah ee daroogada si xun u isticmaal (Leshner, 1997). Neuroplasticity waxaa loo maleynayaa inay dhexdhexaadinayso saameynta soo-gaadhista noocan oo kale ah (Nestler, 2001). Nidaamyada xasaasiga ah ee maskaxda dopamine (DA) waa nooc ka mid ah neuroplasticity oo lagu soo rogay firfircoonida dusha sare ee dhaqdhaqaaqa qaboojinta (CS) ee daroogada, iyo raadinta daroogada khasabka ah (Robinson iyo Berridge, 2001). Feejignaanta waxaa si kumeel gaar ah loogu qeexay by sii deynta DA iyada oo laga jawaabayo CS abaalmarinta iyo kordhinta jawaabta jaangooyooyinka ee loo adeegsado DA-da (Robinson iyo Berridge, 1993; Piired iyo Kalivas, 1997; Vanderschuren iyo Kalivas, 2000). In kasta oo feejignaantu ay tahay mid keliya oo isbeddello maskaxeed oo badan oo lala xiriirinayo balwadda (Robbins iyo Everitt, 1999; Koob iyo Le Moal, 2008), isbedelada ku saabsan sii deynta daawada dopamine sii-deynta ayaa la soo jeediyay inay matalaan neuroadaptations caam ah oo ku lug leh raadinta maandooriyaha ku-saleysan (tusaale, dib u noqoshada), in daroogooyinka ay kiciyaan dareenka kalsoonida u leh astaamaha (tusaale ahaan, morphine) ama loolanka dhiirrigelinta (tusaale, amphetamine) , waxay kaloo keenaysaa dib u soo celinta jawaabihii firfircoon ee firfircoon ee halyeeyga ama is-maamulka kookaha - oo ah nooc xayawaan ah oo dib u laabasho ah (Vanderschuren et al., 1999). Caddeymo muujinaya dhiirrigelin dhiirrigelin (kordhinta qiimaha abaalmarinta daroogada) ayaa inta badan lagu dhawaaqayaa ka dib soo-gaadhista bilowga ah ee daroogada qabatimadu waxay sidoo kale soo jeedineysaa in feejignaanta laga yaabo inay ku lug yeelato marxaladaha hore ee balwadda (Vanderschuren iyo Pierc, 2010).
Khamaarka jir ahaaneed (PG) waxaa lagu tilmaamay inuu yahay qabatinka dabeecada isla markaana dhowaan dib loogu soo celiyay isla isla jaangooyooyinkii ku tiirsanaanta walaxda ee qaybta 5th ee Buugga Baadhitaanka iyo Tirakoobka Tilmaamaha Xanuunnada Maskaxda (Frascella et al., 2010; APA, 2013). Tani waxay muujineysaa in PG ay ka dhalan karto soo ifbaxid joogto ah oo ku saabsan waxqabadka khamaarka, in hababka caanka ah ay u dhexdhexaadin karaan saameynta khamaarka iyo soo-gaadhsiinta maandooriyaha (Zack and Poulos, 2009; Leeman iyo Potenza, 2012); iyo in dareenka maskaxda ee maskaxda DA laga yaabo inuu noqdo mid muhiim u ah nidaamkaan.
Caddaynta kiliinikada ayaa si aan toos ahayn u taageerta suurtagalnimada: Isticmaalka positron emmo tomography (PET) Boileau iyo asxaabtu waxay ogaadeen in maadooyinka PG raggu ay si weyn u muujinayaan sii deynta 'DA' iyada oo laga jawaabayo amphetamine (0.4 mg / kg) marka loo eego xakamaynta ragga caafimaad qabta (Boileau et al., 2013). Guud ahaan kala duwanaanshaha kooxda ayaa muhiimad weyn ka lahaa iskaashatada iyo isku xidhka somatosensory. Wadada loo yaqaan 'limbic striatum', oo ay kujirto qanjirada Nucleus-ka, kooxaha ma kala duwana. Si kastaba ha noqotee, maadooyinka PG, DA lagu sii daayo limbic striatum waxay toos ula xiriirtaa darnaanta calaamadaha PG. Natiijooyinkaani waxay la jaan qaadayaan dareenka maskaxda ee wadooyinka maskaxda ee PG, laakiin waxay sidoo kale soo jeedinayaan kala duwanaansho muhiim ah oo la xiriira shakhsiyaadka ku tiirsan walxaha aadanaha iyo nooca xayawaaniga caadiga ah ee dareenka amphetamine. Si ka duwan maaddooyinka PG iyo xayawaanka u soo qaatay qiyaasta hoose ee amphetamine (cf. Robinson et al., 1982), bini'aadamka ku tiirsan sunta ayaa si isdaba joog ah u muujisay DA u soo daynta loollan dhiirigelin leh (Volkow et al., 1997; Martinez et al., 2007), iyo caddeyn ka timid xayawaanku waxay muujinayaan in tan laga yaabo inay ka tarjunto hoos u dhac ku yimid shaqada DA inta lagu guda jiro marxaladaha bilowga ah ee ka fogaanshaha waxyaabaha la xiriira isticmaalka mukhaadaraadka (Mateo et al., 2005). Daraasadaha lagu sameeyay xayawaannada kicinta dareen-kicinta ee xayawaanada, sii-daynta sii-daynta DA ayaa badiyaa lagu arkaa xaddiga loo yaqaan 'limbic striatum' halkii laga saari lahaa xaddiga 'isuduwaha', somatosensory) striatum (Vezina, 2004). Si kastaba ha noqotee, faaqidaadinta (sida, xaalad ku jirta) raadinta daroogada ee xayawaanka si isdaba joog ah ugu soo ifbaxay maandooriyaha ayaa lala xiriiriyay sii deynta DA ee kujirta xudunta, natiijada loo maleynayo inay muujineyso qaab dhaqan xumo badan leh (Ito et al., 2002). Markaa, sare u qaadista guud ee DA ee lagu sii daayo gobollada durugsan ee maaddooyinka PG waxaa laga yaabaa inay la xiriirto abaalmarin ku saleysan qaab-dhismeedka (aan dabacsanaan lahayn, jaangoyn u lahayn) raadinta ku lug leh "horumar ka socda marinka hore iyo qeybaha dambe ee duruufaha" (Everitt iyo Robbins, 2005, p. 1481), halka DA sii-deyn la'aanta ah ee sii-dayntu ay ku jirto miisaan-yada kumbuyuutarrada mawduucaani ay si toos ah ugu habboon tahay dareenka dhiirigelinta sida caadiga ah loogu qaabeeyo xayawaanka. Natiijooyinka baaritaanka PET ma sheegi karaan in DA-da fal-celin-la'aaneed uu yahay qaab horay u jiray maaddooyinka PG-da, natiijada khamaarka, ama natiijada qaab kale oo gebi ahaanba ah. Si aad uhesho su'aashan, waxaa lagama maarmaan ah in la muujiyo ogeysiinta dareen-celinta khatarta khamaarka dabadheeraad ah maadooyinka caadi ahaan ka hor soo-gaadhista. Tani waxay soo saartaa su'aalaha sida ku saabsan qaababka khamaarka ay u badan tahay in ay u nugulaan dareenka.
Skinner wuxuu xusay in jadwalka isbeddelka xoojinta uu aasaas u ahaa khayaanada khamaarka (ama ugu yaraan adkeysigeeda) (Skinner, 1953). Dhaqanka sharadka ee ciyaarta mashiinka ciyaarta ayaa si fiican u waafajinaya mabaadii'da aasaasiga u ah qaboojinta aaladda, sida ka muuqata isfahamka la filayo ee u dhexeeya lacagta lacagta iyo cabirka sharadka ee ku dhaca isdabajoogga (Tremblay et al., 2011). Sidaa daraadeed, adeeg bixiyaha saamiga isbeddelka isbedelka ayaa u muuqda inuu bixinaayo qaab mucjiso ah oo khariidadda khamaaraya.
Daraasad dhowaan la sameeyay xayawaanku waxay bixisaa taageero bilow ah oo xoog leh oo ku saabsan saameynta sababa soo-gaadhista khamaarka dareenka. Fannaanka iyo asxaabta ayaa baaray saameynta 55 1 – h kalfadhiga maalinlaha ah ee go'an (FR20) ama doorsoomaha (VR20) saccharin xoojinta hawlqabadka lever-press operant oo ku saabsan jawaabta xigashada xigta ee qiyaasta hooseysa (0.5 mg / kg) amphetamine-ka ragga. Sprague Dawley) jiirka (Singer et al., 2012). Waxay u maleynayaan in, haddii khamaarka uu keeno dareen-celinta, jiirka oo u muuqda jadwalka ku-meel-gaadhka ah, kaas oo ku takri-falaya khamaarka, waa inuu muujiyaa jawaab weyn oo ku saabsan amphetamine-ka marka loo eego jiirka jaangoo go'an. Sida la saadaaliyay, kooxda VR20 waxay soo bandhigeen 50% jawaab dheeri ah oo laga helo mandheerta amphetamine marka loo eego kooxda FR20. Taa bedelkeeda, kooxdu waxay soo bandhigeen qulqul-celin isku-dhafan ka dib markii lagu muday suuxdin. Natiijooyinkaasi waxay xaqiijinayaan in si joogta ah loo xoojiyo xoojinta isbadelka ku filan in ay u keento kacimad-celin ku wajahan DA-da oo ku wajahan xayawaanada caafimaadka leh ee loo qoondeeyey jadwallada.
Dhowr su'aalood ayaa ka soo baxay natiijadan: Marka hore, illaa heer intee la eg ayaa loo arkaa in ay ku egtahay ama ay ka maqan tahay - inta udhaxeysa jawaabta howl wadeenka iyo natiijadiisa dhexdhexaadinaysa waxyeeladaan? Erayada barashada, saameyntani ma ku lug leedahay “filasho natiijada jawaabta,” ama saameyn la mid ah ayaa lagu arki karaa maqnaanshaha jawaab-bixiye, tusaale ahaan, “filasho natiijada ka soo baxda” qaab dhismeedka Pavlovian (ie Bolles, 1972)? Marka labaad, miyuu ku jiraa xaalad degdeg ah oo udhaxaysa dhacdadii kicinta (jawaab ama kicin) iyo natiijadiisu saameyn ku yeelato heerka dareenka?
Su'aasha labaad waxay ka hadlaysaa doorka aan hubin ee dareenka. Tusaale ahaan, sameeyaan ciyaaraha natiijada dhabta ah ee aan si aan la filaynba loo kala saari karin - waxay leeyihiin karti weyn oo ay ugu nugul yihiin dareenka ciyaaraha marka ay ku guuleystaan guusha ay ku guuleysteen laakiin si aan kala duwaneyn, xitaa haddii heerka qiimaha rasmiga ah uu hooseeyo? Cilmi-baaristaani waxay ka jawaabtay su'aalahan.
Naqshadeynta tijaabada waxaa lagu ogeysiiyay daraasad seminal ah oo ku saabsan abaalmarinta iyo abaalmarinta DA neuron ee daanyeerka (Fiorillo et al., 2003). Xayawaanka daraasaddan ayaa helay abaalmarin casiir ah (US) oo hoos yimaada 0, 25, 50, 75, ama 100% jadwalka saamiga. Jadwalka waxaa loo xilsaaray 1 ee 4 CS (kala duwan). Jadwalka 0% wuxuu bixiyay abaal marin badanaa sida jadwalka 100%, laakiin laga saaray CS. Heerka ka-dillaaca ee DA neurons inta lagu jiro muddadii u dhaxeysay bilowga Hore iyo soo bixinta Mareykanka ama ka-dhaafitaanku wuxuu ahaa qiyaasta ku-tiirsan ee ku-tiirsan. Daraasadu waxay ogaatay in jawaabta DA kordhisay ayadoo la adeegsanayo hubin la'aanta bixinta abaalmarinta. Sidaa darteed, hoosta 100% jadwalku wuxuu kobciyey dhaqdhaqaaq yar, oo hoos imaanaya jadwalka 25 iyo 75%, CS wuxuu soo saarey heer dhexdhexaad ah oo isku mid ah oo waxqabadyo ah, iyo jadwalka 50% jaangooyuhu wuxuu ku dhawaaqay waxqabadka ugu badan. Xaalad kasta, heerka dabka ayaa sii kordhay muddada CS-US ee dhexdhexaadinta, taas oo ah, sida rajadu soo dhawaato miro.
Natiijooyinkaasi waxay muujinayaan in hawlaha DA-da kaliya aysan ku kala duwaneyn haddii ama abaal-marintu ay tahay mid xaqiiqo ah (Ratio Ratio) ama aan la hubin (Isbeddelka Isbedelka), laakiin sidoo kale waxay ku kala duwan yihiin qaddarka macluumaadka ku saabsan bixinta abaalmarinta CS-ga. 100% xaalad, CS waxay soo bandhigaysaa rajada abaalmarinta iyo sidoo kale si fiican u saadaalisa bixinteeda. 25 iyo 75% shuruudaha, CS waxay soo bandhigtay rajada, waxaana ay saadaalineysaa bixinta abaalmarinta seddex jeer afar jeer. 50% shuruudaha CS wuxuu soo bandhigayaa rajada laakiin wuxuu bixinayaa wax macluumaad ah oo ku saabsan bixinta abaalmarinta wixii ka baxsan oo keliya. Iyadoo ku saleysan natiijooyinkooda, Fiorillo et al. ayaa lagu soo gabagabeeyay: "Kororka bukaanka ee kor u kaca ee dopamine wuxuu gacan ka geysan karaa sifooyinka wanaagsan ee khamaarka" (p. 1901).
Saamaynta 50% abaalmarinta isbeddelka ee kalfadhi keliya waa inaysan isbeddelin inta lagu gudajiro kalfadhiyo badan maxaa yeelay suuragalnimada abaalmarintu weli waa mid aan gebi ahaanba la saadaalin karin maxkamad kasta. Sidaa darteed, markaad tixgelinayso xaaladaha kordhin kara firfircoonida joogtada ah ee DA neurons ee dhacdooyinka soo noqnoqda ee khamaarka 50% jadwalka waa inuu keenaa kan ugu waara iyo sidoo kale saameynta ugu xoogan. Tani waa mid xusid mudan marka la fiiriyo heerka muddada dheer ee abaalmarinta (bixinta> 0) ee lagu arkay kumanaan kun oo wareegyo ah oo ku saabsan mashiinka ganacsiga ayaa ahaa 45.8% (Tremblay et al., 2011). Sidaa awgeed, abaalmarinta 50% waxay muujinaysaa inay si sax ah u muujineyso jadwalka mushaharka ee ay maamusho qalabka khamaarka ee dhabta ah.
Daraasadda hadda jirta waxay adeegsatay jadwallo isku mid ah sida Fiorillo et al. soo-gaadhis joogto ah, oo udhaxeysa kooxaha 'naqshadeynta jiirka. Xayawaanku waxay soo mareen ~ 3 toddobaad oo kal-fadhiyo maalinle ah, halkaas oo CS (nal) lagu lammaaneeyey Mareykanka (qadar yar oo sukrose ah). Marxaladda tababarka ka dib, xayawaanku way nasteen ka hor qiimeynta dareenka oo lagu muujiyey jawaab celinta tareenka ee amphetamine. Iyada oo ku saleysan suugaanta, waxaa la saadaaliyay in jiirka u nugul jadwalka abaalmarino kala duwan uusan ku kala duwanaan doonin dhaqankooda dhaq dhaqaaqa tareenka ee daroogada ah laakiin wuxuu soo bandhigayaa heerar aad u kala duwan oo dhaq dhaqaaqa ka dib amphetamine, iyadoo kooxda 50% ay soo bandhigayaan jawaab celin weyn ee tareenka ee qaraabada. kooxaha kale muddada qaadashada, qaab la filan karo haddii xoolaha 50% horey loogu soo bandhigi lahaa qadar dheeri ah oo amphetamine lafteeda ah (yacni, iskutallaab-dareen).
tijaabi 1
Qalabka iyo hababka
maadooyinka
Afar kooxood (n = 8 / koox) oo qaangaar ah (300-350 g) ragga Sprague-dawley (Charles River, St. Constant, Quebec, Canada) ayaa si gooni ah loogu hayaa sanduuqyada polycarbonate (20 43 × 22 cm) hoosta 12: 12 wareega iftiinka madow. Waxay heleen ad libitum helitaanka cuntada iyo biyaha, iyo maaraynta maalinlaha ah ee tijaabiyaha toddobaadyada 2 ka hor daraasadda. Koox kasta ayaa lagu sharxay mid ka mid ah jadwalka abaalmarinta doorsoomayaasha: 0, 25, 50, ama 100%. Kooxda 75% ayaa laga saaray daraasaddan bilowga ah, sida Fiorillo et al. (2003) waxaa laga helay soosaarid post-CS DA oo u dhiganta jadwalka abaalmarinta 25 iyo 75%, taas oo ah in labada shuruudood ay horseedeen sii deyn DA oo ka weyn sidii ay ahayd xaalada '100% CS-US', laakiin ka yar heerka 50%.
nabadgelyada
Helitaanka bandhigyada sukrose iyo CS waxa loo siiyaa shakhsi ahaan sanduuqyada wax qabadka (33 × 31 × 29 cm). Sanduuq kastaa wuxuu ku yaalaa majaladda xoojinta, oo ku yaala derbiga hore. Iftiinka sare ee majaladda waxaa loo adeegsaday CS. Qalabka dareeraha, kontoroolka solenoid ee xakamaynta ayaa laga yaabaa inuu kor u kaco dabaqa saxaafadda. Dhacdooyinka sanduuqa waxaa xakamey qalabka Med Associates qalabka iyo software, iyadoo la adeegsanayo barnaamijka gudaha ku qoran MED-PC. Imtixaanka Locomotor waxaa loo qabtaa si gooni gooni ah baqashada Plexiglas (27 × 48 20 cm). Kafaar kasta wuxuu ku rakiban yahay nidaam lagu kormeerayo oo ka kooban lix unug oo sawir-gacmeed si loo ogaado dhaqdhaqaaqa wareega.
Nidaamka
Tababarka. Daraasada waxaa lagu fuliyay si waafaqsan xeerarka anshaxa ee ay dejisay Golaha Kanadiga ee Xanaanada Xoolaha. Jirradu waxay ahaayeen kuwo xaddidan 90% miisaankooda jirkooda muddada daraasaddan oo ay degganaayeen shakhsi ahaan. Tababar kasta wuxuu helay maalmaha 15 ee tababarka abaalmarinta Sucrose (10% xal biyaha ah ee 0.06 ml kasta): 5 maalmo isku xigta x toddobaadyo 3, maalmaha fasaxa ah. Xayawaanka ayaa lagu hayaa qiyaas caadi ah ka hor iyo ka dib marxaladda tababarka; Xirmooyinka suufiyadu waxay xaddidan yihiin shan iyo toban ~ 40-min tababaro. Maalin kasta oo maalin kasta ah waxay ka kooban tahay bandhigyada dhiirigelinta 15 (iftiin, CS), mid kasta oo u dhaxeeya isku-dhexaadin dhexdhexaad ah oo ah 120 s. Iftiinka wuxuu ku yaalaa qaybta sare ee majaladda, waxana uu ku sugnaa 25, oo leh sukrose laga helo intii lagu jiray 5-da ugu dambeeyey. Xaaladda kooxda 0 ee dermerka sukrose waxaa la sara kiciyey 140 kasta (loogu talagalay 5 s), laakiin iftiinka kicinta ayaa aan iftiimin. Tani waxay u dhigantaa dhexda u dhexeeya bandhigyada dipper ee kooxda 0 iyo kooxaha kale (120 + 25 s). Xilliga daaweynta kasta way socotay ~ 40 min. Celcelis ahaan, kooxda 25 waxay heshay sukrose markasta afartii afartan midoodba; Kooxda 50 waxay heshay sukrose hal labadii bandhig ee CS, kooxdan 100 waxay heshay sukrose kaddib bandhig kasta oo CS.
Imtixaanka. Laba toddobaad kaddib marka la soo galo galitaankii ugu dambeeyay (ama "xaaladdan"), jawaabta locomotor ee d-amphetamine (AMPH; ip) ayaa la qiimeeyey. Jiirka waxaa la siiyay seddex seddex xummo-saac ah si ay ugu habboonaadaan sanduuqyada lafdhabarta, oo ay ku xigaan lix kalfadhi imtixaan AMPH ah. Maalmaha tijaabada AMPH waxay ka dhaceen xilliyada 2-wk. Maalmaha imtixaanka, jiirka ayaa la siiyay 1 min si loo ogaado sanduuqyada kadibna waxay heshay hal xinmood mg / kg oo AMPH ah oo la raacay, kalfadhiyo gooni gooni gooni ah, shan jeer oo 30 mg / kg ah (hal qiyaas maalintii) maalmaha imtixaanka 0.5 illaa 1.0 . Maqnaanshaha Kadib-AMPH waxaa lagu qiimeeyay 1 min halkii kulan kasta.
Habka falanqaynta xogta
Falanqaynta tirakoobka waxaa lagu sameeyey SPSS (v. 16 iyo v. 21; SPSS Inc., Chicago IL). Jawaabta dhaqdhaqaaqa degdegga ah ee CS-ga ayaa lagu qiimeeyaa marka la eego dhuunta sanka ah ee dillaac halkaas oo sukrose la faarujiyey. Tirada celceliska sanka sanka inta lagu guda jiro interval (5 s trial) ayaa markaa la barbardhigay tirada sanadka ee sanka ee mudada isku mid ah (5 s) celceliska wakhtiga CS ka maqnaa. Kooxda Qeybta xaadirka ah ee ANOVAs ee sanka-sanadka leh ee CS joogta iyo maqnaanshaha ayaa raadinayay helitaanka kala-takoorka ee ka jawaab celinta jawaabta caleenta iyo sanqadarada aan kala sooc lahayn ee hoos yimaada jadwalka kala duwan ee koorsada tababarka 15 sucrose.
Saameynta daaweynta jawaabaha lafdhabarta waxaa lagu qiimeeyay Kooxda Qalinjebinta ANOVA ee marxaladda daaweyn la'aanta bilaashka ah (saddex kalfadhi), pre-sensitization 0.5 mg / kg tartan AMPH (hal kulan), iyo inta lagu guda jiro shanta sano ee 1 mg / kg AMPH marka la eego qaababka xasaasiga ah, marka kooxaha la filayo inay ku kala duwanaadaan jawaab celinta qiyaasaha soo noqnoqda AMPH. Kooxda Xidhiidhka ANOVAs waxay sidoo kale qiimeeyeen jawaabaha lafdhabarta ee daawooyinka aan xagjirnimada lahayn intii lagu jiray 30-min ee xeeldheeraanshaha horay laysku duro oo laga soo qaaday kulan kasta ee imtixaanka AMPH. Isbarbardhiga la qorsheeyay ayaa qiimeeyey farqiga ujeedka celceliska kooxda 50 iyo kooxda 0 (ma laha xakamaynta filashada) iyo kooxda 100 (ma jiro xakameyn aan hubin) t-tests (Howell, 1992), adoo u isticmaalaya qaladka MS iyo shuruudaha qaladka df ee saameynta ku habboon (tusaale ahaan, koox ama koox × isdhaxgalka kulanka) kana socda ANOVA (Guul, 1971). Falanqaynta isbeddellada "Polynomial Trial" waxay tijaabiyeen isbedelka ku saabsan koorasyada koorsada.
Si loo go'aamiyo haddii jawaabta suura galka ah ee maqnaanshaha iyo maqnaanshaha CS inta lagu guda jiro 15 Sucreoska Tababarka tababarada ayaa wax ka beddelay jawaab celinta locomotor ee AMPH, ama dhexdhexaadinta koox dhexdhexaad ah AMPH, falanqaynta dabagalka ee khilaafka (ANCOVAs) ayaa lagu sameeyey AMPH xogta locomotor, oo ay ku jiraan sanka oo dhan sanqadha (miisaanka loogu talagalay fadhiyada 15) marka CS ka maqnayd sida iswaafaq. Saameyn muhiim ah oo ku saabsan dareenka ayaa muujinaya in jawaabta daroogo la'aanta ah ee loo xakameynayo dhexdhexaadka ah (saameyn ku yeelatay awoodda) saameynta kooxda ama kooxdu. Hoos-u-dhac ku yimaada saameynta kooxda ama kulankooda joogitaanka isbeddel weyn ayaa tilmaamaya in jawaabaha hababka ay dhexdhexaadinayaan (xisaabiyeen) saameynta kooxda ama kulanka. Hoos-u-dhaca muhiimadda kooxda ama saamaynta fadhiga ee maqnaanshaha saameyn weyn oo dhexdhexaad ah waxay muujineysaa in lumay awoodda tirakoobka sababtoo ah dib-u-soo-celinta df ee ereyga qaldan ee loo yaqaan 'dialariate', oo aanaan ku dhicin fasiraadda saameynta kooxda ama kulanku.
Natiijooyinka
Sigaarka sanka inta lagu jiro kalfadhiyada qaboojinta sukrose
CS joogta. Jaantuska Jaantus1A1A waxay muujinaysaa sanadka sanadka ee 25, 50, iyo 100 halka CS-du ay joogeen 15 Shukulaatooyinka Sukrose (sanqadha sanka looma codsanin kooxda 0, oo aan helin CS). Kooxda 3 × 15 ANOVA waxay soo saartay saameyn weyn oo muhiim ah ee Kooxda, F(2, 21) = 5.63, p = 0.011, iyo Kulanka, F(14, 294) = 14.00, p <0.001, oo ay weheliso is-dhexgal kal-kooxeed muhiim ah, F(28, 294) = 2.93, p <0.001. Jaantus Jaantus1A1A waxay muujineysaa in saameynta ugu weyn ee Kulanku uu ka muuqanayo kororka sanka sanadka ee dhammaan sedexda kooxood, iyo saameynta ugu weyn ee Kooxda waxay guud ahaan guud ahaan guud ahaan muujineysaa dhibcaha guud guud ahaan 100 iyo kooxda 25 oo leh dhibco dhexaad ah kooxda 50. Koox muhiim ah oo wada-xaajoodka isdhexgalka, F(2, 21) = 4.42, p = 0.030, waxay muujinaysaa kor u kac degdeg ah, qallafsan, iyo diyaargarowga sanka oo ka soo baxa kooxo 100, oo ka soo horjeeda kordhinta tooska ah ee kulamada kooxaha 50, iyo kordhinta toosan ee kulanno kooxeed 25.
CS maqnaanshaha. Jaantuska Sawirka1B1B waxay muujinaysaa sankoodka sanadka ee dhammaan afarta kooxood ee mudada u dhiganta (5 S × 15 trials) celcelis ahaan wakhtiga CS ka maqnaa. Kooxda 4 × 15 ANOVA waxay soo saartay saameyn weyn oo muhiim ah ee Kooxda, F(3, 28) = 7.06, p = 0.001, iyo Kulanka F(14, 392) = 2.84, p <0.001, oo ay weheliso is-dhexgal kal-kooxeed muhiim ah, F(42, 392) = 3.93, p <0.001. Is-dhexgal cashar kooxeed muhiim u ah isbeddelka laba jibaaran, F(3, 28) = 3.91, p = 0.019, oo aan wehelin isdhexgalka ee isbeddelka dhoobada, F(3, 28) <0.93, p > 0.44, ayaa ka muuqatay muuqaalka "rogay-U" ee sanka oo laga dheehan karo fadhiyada kooxda 0, iyadoo ka soo horjeedda guud ahaan xasiloonida kulamada kooxaha kale.
Hab-socodsiinta qolalka hoose
Kooxda 4 3 ANOVA ayaa saameyn weyn ku yeeshay Kulanka, F(2, 56) = 5.67, p = 0.006, iyo saameyn kale oo muhiim ah, F(3, 28) <1.60, p > 0.21. Udub dhexaad u dhigma celcelis ahaan (SE) labadii saac ee sanduuqyada tareenka waxay ahaayeen 2 (1681) kalfadhigii 123, 1 (1525) kalfadhigii 140aad, iyo 2 (1269) kalfadhigii 96. Isbarbardhiga qorshaysan ma helin kala duwanaansho weyn oo udhaxeeya kooxda 3 iyo kooxda 50 ama koox 0 fadhiga koowaad ee ugu dambeeya ama ugu dambeeya, t(84) <1.69, p > 0.05. Sidaa darteed, maqnaanshaha AMPH, soo-noqnoqoshada soo noqnoqda ee sanduuqyada imtixaanka waxay la xiriirtay hoos u dhac joogto ah oo ku yimaada dhaqdhaqaaqa dhaqdhaqaaqa dhaqdhaqaaqa ee afarta koox (sida, Saameynta Kalfadhiga), iyo wax jawaab ah oo kaladuwan oo ah shaqeynta jadwalka tababarka sukrose (isdhexgal la'aan) .
Kulanno tijaabo ah
Saameynta horay u dareemeyn 0.5 mg / kg tartan AMPH.
Maqnaanshaha hore ee cirbadeynta. 4 Group hal dhinac ANOVA ee jawaab celinta locomotor inta lagu guda jiro 30-diyaargarowga xuddunta horay loo dejiyey ayaa wax saameyn ah u lahayn, F(3, 28) <1.05, p > 0.38. Isbarbardhiga la qorsheeyay ma helin farqi weyn oo u dhexeeya kooxda 50 iyo kooxda 0 ama kooxda 100, t(32) <0.87, p > 0.40. Sidaa darteed, kala duwanaanta aasaasiga ah ee dhaqdhaqaaqa kahortaga kahor ma aysan xisaabin kala duwanaanshaha kooxeed ee jawaab celinta tareenka ee AMPH. Kala-goysyada birta ah ee celceliska (SE) ee saamiga ayaa ahaa 559 (77).
Maqnaanshaha dhejis la'aanta ka-dib-u-qaadista iyo kulamadii ugu dambeeyay ee aan la-isticmaalin daroogada. Kalfadhiga 4 Group AN 2 ANOVA ayaa isbarbar dhig ku sameeyay jawaab celinta kooxaha ee ku saabsan fadhigii ugu dambeeyay ee habeynta, isla markaaba ka dib markii la ogaaday kahortaga 0.5 mg / kg AMPH. Dhibcaha fadhiga habeynta (120 min) ayaa loo qoondeeyay inay u dhigmaan muddada kalfadhiga imtixaanka AMPH (90 min) (dhibcaha habeynta cayriin × 90/120). Falanqaynta waxay keentay saameyn weyn oo muhiim ah Kalfadhiga, F(1, 28) = 34.16, p <0.001, oo aan lahayn saameyn kale oo muhiim ah, F(3, 28) <2.26, p > 0.10. Saameynta Kalfadhigu waxay muujisay kororka macnaha (SE) jajabka dogobyada jawaabta qiyaasta, laga bilaabo 952 (72) ilaa 1859 (151). Isbarbardhiga la qorsheeyay ma helin faraq weyn oo u dhexeeya kooxda 50 iyo kooxda 0 ama kooxda 100 ee ka jawaab celinta qiyaasta, t(56) <1.72, p > 0.10. Si kastaba ha noqotee, amarka darajada dhibcaha jebinta dogob (M; SE) oo la jaanqaaday mala awaalka: kooxda 50 (2205; 264)> koox 0 (2025; 203)> koox 100 (1909; 407)> koox 25 (1296; 299) .
Saameynta 1 mg / kg AMPH.
Maqnaanshaha hore ee cirbadeynta. 4 Group 5 Kulanka 30 ANOVA ee jawaab celinta mandiigada inta lagu guda jiro 1-diyaargarowga horudhac horudhac ah oo lagu sameeyo XNUMX mg / kg AMPH tijaabo ah waxay saameyn weyn ku yeesheen Kulanka, F(4, 112) = 43.64, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(3, 28) <0.97, p > 0.42. Isbarbardhiga la qorsheeyay ma helin farqi weyn oo u dhexeeya kooxda 50 iyo kooxda 0 ama koox 100 kulankii ugu horreeyay ama kan ugu dambeeya, t(140) <0.84, p > 0.30. Sidaa darteed, kala duwanaanshaha aasaasiga ee tareenku ma uusan xisaabtamin kala duwanaanshaha kooxeed ee jawaab celinta tareenka ee AMPH. Dhibcaha jebinta dogobka celceliska (SE) ee wajiga habeyn-qaadashada hore ee kal-fadhiyada 1-5 waxay ahaayeen: 454 (30), 809 (53), 760 (36), 505 (35), 756 (39).
Mishiinka laf-dhabarka kadib. Jaantuska Jaantus22 waxay muujineysaa saameynta shan cirbadood 1 mg / kg AMPH (mid asbuucii) oo ah dhibcaha dhaqdhaqaaqa lafdhabarka ee afarta kooxood. Kooxda 4 5 ANOVA ayaa saameyn weyn ku yeeshay Kulanka, F(4, 112) = 8.21, p <0.001, oo ah saamaynta ugu yar ee kooxda, F(2, 45) = 3.28, p = 0.085, iyo wax wada-shaqayn la'aan ah, F(12, 122) <0.77, p > 0.68.
Isbarbardhigga qorshaysan ayaa shaaca ka qaaday in dhibcaha kooxda 50 ay si weyn uga duwan yihiin kooxda 0, t(14) = 2.19, p = 0.037, iyo kooxda 100, t(14) = 2.36, p = 0.025 [oo si aan kala duwaneyn uga duwan kooxdan 25, t(14) = 2.03, p = 0.051]. Sidaa darteed, kooxda 50, jawaabta locomotor ee 1 mg / kg AMPH ayaa si ka baxsan u saameeyay saddexda kooxood ee dhammaan shanta baaritaan. Falanqaynta isweydaarsiga polynomijiga ayaa lagu ogaaday isbeddel weyn oo dhexdhexaad ah, F(1, 28) = 32.47, p <0.0001, oo aan lahayn isbeddello kale oo muhiim ah F(1, 28) <1.78, p > 0.19. Jaantus Jaantus22 waxay muujineysaa in natiijadan ay ka muuqato qaab "U-rog" Ujeedooyinka oo dhan.
Xakamaynta isbeddelka sanka sanka ee wax ka qabashada tababarka sukrose
Dabagalka ANCOVA ee jawaabaha locomotor ee 1 mg / kg AMPH, oo leh sanka sanka (CS fadhiga) sida muuqaalka, saddexda kooxood ee hela CS, ayaa saameyn weyn ku yeeshay kooxda, F(2, 20) = 3.07, p = 0.069, iyo wax saameyn ah oo aan la taaban karin, F(4, 80) <0.05, p > 0.85. Sidaa awgeed, habka loo maro jawaabta inta lagu jiro tababarka ma uusan sharxin kala duwanaanshaha weyn ee jawaabta tareenka ee 1 mg / kg AMPH ee kooxaha 25, 50, ama 100.
Dabagalka ANCOVA ee jawaabaha locomotor ee 1 mg / kg AMPH, oo leh sanku (CS oo maqan) sida dareenka, ayaa saameyn weyn ku yeeshay nooca daawada, F(1, 27) = 6.17, p = 0.020, saameyn weyn oo weyn ee kooxda, F(3, 27) = 4.13, p = 0.016, Kulan aan caadi ahayn × Isdhexgalka isweydaarsiga, p = 0.080, iyo saameyn kale oo muhiim ah, F(4, 108) <1.48, p > 0.21. Sidaa darteed, habka aan loo cunin (aan kala sooc lahayn) ee ka jawaab celinta inta lagu jiro tababarka wuxuu sharraxay kala duwanaansho weyn oo ku yimid jawaabta tareenka ee 1 mg / kg AMPH. Si kastaba ha noqotee, kala duwanaanshahani wuxuu ahaa mid aan is dulsaarin kala duwanaanta kooxeed, maxaa yeelay ka mid noqoshada isbeddelka falanqaynta ayaa kordhay halkii laga yareyn lahaa muhiimadda saameynta kooxda.
Dood
Xogta qanjirada sanka marka CS-yada ay joogaan waxay muujinayaan in kooxuhu ay ku biireen ururka iskaashiga u dhaxeeya CS iyo sukrose sida ay ka muuqato korodhka jawaabaha la soo bandhigay ee ku saabsan kulamada tababarka. Faahfaahinta jawaab-celinta kulannada halka CS-du joogi lahaa waxay soo jeediyeen in 100 iyo 50% jadwalka CS-US ay si isku mid ah waxtar ugu yeesheen habka loo soo jeediyo, halka jadwalka 25% ay ka soo baxeen hab korodhsiimo ah oo ku saabsan habka loo yaqaan 'cue-induced'. Xogta sanka ee sanka inta uu CS ka maqan yahay waxay soo jeedinaysaa in kooxihii helay seddexda jadwalka tababarka CS-sukrose (kooxda 25, 50, 100) si dhakhso ah u barteen inay yareeyaan sankooda sanadka marka laga reebo CS, halka xayawaanka kooxda 0 , oo aan helin CS, waxay barteen oo kaliya in ay yareeyaan dabeecadooda ku wajahan si xaddidan ka dib markii tababar ballaaran.
Xogta degnaanshaha waxay muujineysaa in kooxuhu aysan kala duwaneyn AMPH ka dibna soo noqnoqodka soo noqnoqda sanduuqyada baaritaanka waxaa lala xiriiriyay jawaab celinta lafdhabar la'aanta ah ee daroogada. Sidaa daraadeed, kala duwanaanta kooxaha dhexdooda iyo kordhinta jawaab celinta qiyaasaha daaweynta AMPH ee aan la soo celin karin looma xisaabin karo farqiyada hore ee jira ee dhaqanka lafdhabarada.
Natiijooyinka ka hortagga cilladda hor-u-marinta ee 0.5 mg / kg AMPH ayaa xaqiijiyay in daroogadu kordhiso dhaqdhaqaaqa firfircoon ee ku salaysan maalinta ugu dambeysey ee aan dawo lahayn. Iyadoo la raacayo aragtida, kooxda 50 waxay ka sarreysaa kooxaha 0 ama 100 (iyo sidoo kale kooxda 25) marka la eego celceliska jawaab celinta qiyaasta, inkastoo farqiga u dhaxeeya kooxaha udhaxeeya muhiim maahan.
Kulamada xasaasiga ah, isbarbardhiga kooxaha udhaxeeya waxay muujiyeen in soo-gaadhistii hore ee 50% abaalmarinta sukrose-ka ay horseeday koror weyn oo ku yimid jawaab celinta socodka si loo helo 1.0 mg / kg qiyaasta amphetamine marka loo eego saddexda jadwal ee kale. Saameyntani waxay ka muuqatay qiyaasta ugu horreysa mana aysan ku beddelin si qaddarin badan oo soo noqnoqday. Falanqaynta isbeddelka ayaa muujisay jawaab-celinta biphasic (muunadda buuxda) ee qiyaasaha soo noqnoqda ee AMPH, kordhinta ilaa qiyaasta saddexaad iyo hoos udhaca intaas ka dib. Natiijooyinka la socoshada ANCOVA oo leh sanka-sanka (CS maqnaanshaha) sida isweydaarsiga ayaa xaqiijiyay in kala duwanaanshaha afarta kooxood ee jawaabaha dhaqdhaqaaqa 1 mg / kg AMPH aan lagu dhexdhexaadin habka aan cuni karin ee ka jawaabaya inta lagu jiro kal-fadhiyada tababarka sukrose.
Saameynta kooxdu inta lagu jiro kalfadhiyada xasaasiga ah waxay ku xirantahay sharraxadeena. Saamaynta ficil-ka-qaadashada bi-phasic ma ahan mid la socota sii socoshada sii socota ee sii socota ee jawaabaha locomotor ee leh qiyaasaha AMPH ee soo noqnoqda. Tani waxay la xiriiri kartaa mudista qaadashada. Si wax looga qabto arrintan, habka (nidaamyada maalinlaha ah ee beddelka ah) oo lagu muujiyay inay si joogto ah u kicinayaan jawaabta locomotor ee jawaabta 1.0 mg / kg ee AMPH (ie, dareenka habdhaqanka) waa in la shaqeeyaa. Saameynta astaamaha xasaasiga ah ee AMPH oo ku saabsan jawaabcelinta dambe ee xallinta labaad ee 0.5 mg / kg waxay sii wadi doontaa taageerada guud ee waxtarkaas. Ka mid noqoshada tartanka salineingka ka hor AMPH waxay go'aan ka gaari doontaa doorka sugitaanka ama cirbadaha la xidhiidha (tusaale ahaan, cadaadiska) saameyn ku yeelashada jawaab celinta locomotor ee AMPH. Ka mid noqoshada 75% Xaaladda Sucreose waxay ku caawineysaa in la caddeeyo doorka abaalmarin la'aanta iyo abaalmarinta naaqnaanta qaabka jawaabaha kooxaha 50 iyo kooxda 25. Intaa waxaa dheer, in loo ogolaado qiimaynta (ANCOVA) ee ku deeqidda jawaab celinta habka loo qiimeeyo daroogada oo loo yaqaan "AMPH" (AMPH) wuxuu ku jiray afar kooxood oo kale (ie, sidaas daraadeed sanka sanka oo dhan oo ka mid ah shan kooxood - oo ay ku jiraan kooxda 0 ee aan helin CS-waxaa lagu dari karaa falanqaynta kala-qaadista CS-ka sida ku cad tusmada). Dib-u-habeyntaas waxaa lagu dhex daray tijaabada 0.
tijaabi 2
Qalabka iyo hababka
Habka tijaabada 2 wuxuu la mid ahaa tii tijaabada 1 laakiin waxaa dib loo eegay si kufiican qiyaas ahaan nidaam la helay si loogu kalsoonaan karo kicinta dareenka AMPH (Fletcher et al., 2005). Isbedelada waxay ahaayeen sidan soo socota: (a) Kooxda 75% CS-sucrose (n = 8) ayaa lagu daray; (b) Inta lagu jiro tababarka sukrose, jiir (marka laga reebo kooxda 0) waxay heshay 20 CS (iftiin) bandhigyo (oo ka soo horjeeda 15 ee tijaabada 1); (c) Shaxda CS waa mid kasta oo isku dhafan dhexdhexaad dhexdhexaad ah ee 90; inta u dhaxaysa: 30-180 (oo la mid ah 120 ee tijaabada ah 1), taas oo ka dhigaysa kororka tababbarada tababarka si loo simo mudada tababarka kasta ee tababarka 1; (d) muddada mid kasta oo ka mid ah sadexdii kulan ee habitimiinta ayaa laga dheehnay 120 ilaa 90 min si ay ula socdaan mudada baaritaanka; (e) Dhibaato (saliid, xNUMX ml / kg) tartan (1 min) ayaa lagu daray (maalinta tababarka Sancro-Xaqiiqo ee 90), si loo qiimeeyo saameynta burqsiga ee duritaanka per se (tus., rajada, walbahaarka); (f) Kulamada 1 mg / kg waxay ku qabteen maalmaha caadiga ah ee usbuuca (maalmaha tababbarka tababarka 12-21) halkii aan isbeddel wiigiiba ah sida tijaabada 1; (g) Iyadoo la socota 0.5 mg / kg AMPH (tababar maalin kadib) 9 mg / kg tartan AMPH ayaa lagu daray (maalinta tababarka dambe ee 0.5), si loo tijaabiyo guud ahaan saameynta xasaasiga ah ee qiyaasta daawooyinka; (h) sanqadha sanadka marka CS-yada la joogo ayaa loo codsaday dhammaan kooxaha (oo ay ku jiraan kooxda 28); (i) sanqadha sanadka marka CS maqnaanshaha ayaa si gaar ah looga diiwaangeliyey bilowga 0-ga isla markiiba ka hor inta aaney bilaabin CS-yada si loo soo bandhigo habka hore uga jawaab celinta.
Natiijooyinka
Sigaarka sanka inta lagu jiro kalfadhiyada qaboojinta sukrose
5 Group x XUMADA 15 2 Heerka XNUMX (CS joogta, CS maqnaanshaha) ANOVA ee sanka sanka ayaa keenay saameyn weyn oo muhiim ah ee Kooxda, F(4, 19) = 2.89, p = 0.050, Casharka F(14, 266) = 2.28, p = 0.006, iyo wejiga, F(1, 19) = 14.72, p = 0.001, iyo sidoo kale isdhexgalka saddex-hab ee muhiimka ah, F(56, 266) = 1.38, p = 0.050. Guddiyada (A, B) Jaantuska Jaantus33 qorshee dhibcaha dhibcaha sanka ee kooxaha CS iyo wejiyada maqnaanshaha CS, siday u kala horreeyaan. Isbarbardhiga labada dhinac waxay muujineysaa in saameynta ugu weyn ee Wajiga ay ka muuqato guud ahaan jawaabaha sanka ee sanka markii CS la joogo iyo maqnaanshaha. Sidaa darteed, jawaabaha cuudka ayaa si aad ah uga dhacay marar badan marka loo eego jawaabihii aan dhaqsaha lahayn. Saamaynta ugu weyn ee Kooxda iyo Fadhiga si sahal ah looma fasirin sababtoo ah isdhexgalka amarka sare. Natiijadan dambe waxay ka tarjumeysay isku soo dhawaanshaha dhibcaha shanta koox oo heer hoose ah oo deggan marka loo eego kulammada markii CS uu maqnaa (Jaantus (Figure3B), 3B), oo ay weheliyaan kala duwanaanshaha dhibcaha sare (Koox 75, koox 100), dhexdhexaad ah (koox 50), iyo hooseeya (koox 0, koox 25) heerarka sanka oo la gooyey oo ka jawaab celiya kulanno marka CS-jir (Figure3A) .3A). Xaaladda hoose ee isbeddellada 'polynomial trend' (linear, semadratic, cubic) oo kaliya isdhexgalka saddexda dhinac ah ee isbeddellada toosan ayaa soo dhawaaday muhiimadda, F(4, 19) = 2.32, p = 0.094, oo ka tarjumaysa kororka guud ee kororka sanka oo ka soo baxa kooxo 75 iyo xasilin deg deg ah oo heer sare ah, dhexdhexaad ah iyo heerar hooseeya oo ka jawaabaya kooxaha kale marka CS-du joogi jiray.
Hab-socodsiinta sanduuqyada cirifoorka
Kooxda 5 3 XIRIIRKA ANOVA ee jawaab celinta xayiraadaha daawooyinka aan xagjiraha lahayn ayaa saameyn weyn ku yeeshay fadhiga, F(2, 70) = 60.01, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <0.70, p > 0.60. Isbarbardhiga la qorsheeyay ee kooxda 50 ee kooxda 0 iyo kooxda 100 ee ku saabsan fadhiyada ugu horreeya iyo kuwa ugu dambeeya ee la qabanayo wax saameyn ah oo muhiim ah ma keenin, t's <0.84, p > 0.40. Sidaa darteed, celceliska jawaab celinta tareenka ee daroogada ee kooxaha muhiimka ah kuma kala duwanaan baaritaanka ka hor. Tirada celceliska (SE) ee jajabka dogobarka 90 daqiiqo waxay ahaayeen 2162 (118) kalfadhigii 1, 1470 (116) kalfadhigii 2, iyo 1250 (98) kalfadhigii 3aad.
Kulanno tijaabo ah
Saline. Kooxda 5 2 Xulashada ANOVA marka la barbar dhigo jawaabaha locomotor ee ku saabsan fadhiga ugu dambeeya ee nafaqeynta iyo fadhiga saline ee tartanka. ANOVA waxay soo saartay saameyn weyn oo ah fadhiga, F(1, 35) = 62.46, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <0.65, p > 0.64. Jaantus Jaantus44 waxay muujinayaan in kooxdu ay macnaheedu tahay oo ay muujinayso in saamaynta fadhiga ay muujinayso hoos u dhac ku yimid jawaab celinta locomotor ee ka soo baxday kulankii kama dambeyska ahaa ee daawada daroogada oo aan loo isticmaalin fadhiga salineing, taas oo aaney kooxdu ku kala duwan tahay. Sidaa awgeed, hoos u dhaca jawaabta locomotor ayaa lagu arkay sedexda kulan ee habituations ayaa ku sii socota daroogada afaraad ee aan la isticmaalin ee sanduuqyada imtixaanka.
Saameynta 0.5 mg / kg AMPH.
Maqnaanshaha hore ee cirbadeynta. 5 Group × 2 Kalfadhiga 30 ANOVA ee xakameynta pre-injirta (0.5-min) ee ka hor iyo ka dib-dareen-celinta XNUMX mg / kg AMPH maalmo tijaabo ah ayaa saameyn weyn ku yeeshay Kulanka, F(1, 35) = 13.39, p = 0.001, iyo saameyn kale oo muhiim ah, F(4, 35) <1.79, p > 0.15. Isbarbardhiga la qorsheeyay ma helin farqi weyn oo u dhexeeya kooxda 50 iyo kooxda 0 ama kooxda 100 fadhigii ugu horreeyay, t(70) <1.00, p > 0.30. Si kastaba ha noqotee, markii labaad (kadib dareenka) kal-fadhiga kooxda 50 (1203; 121) waxay soo bandhigeen si aad u badan oo ka sii horreeya cirbadeynta birta (M; SE) marka loo eego kooxdii 100 (756; 103), t(70) = 5.11, p <0.001, laakiin kama duwana kooxda 0 (1126; 211), t(7) <0.88, p > 0.40. Sidaa darteed, kala duwanaanshaha aasaasiga ee tareenku ma uusan xisaabtamin kala duwanaanshaha kooxeed ee jawaabta tareenka ee qiyaasta ugu horreysa ee 0.5 mg / kg ee AMPH laakiin waxaa laga yaabaa inay gacan ka gaysatay kala duwanaanshaha u dhexeeya kooxda 50 iyo kooxda 100 ee ka jawaab celinta tareenka illaa 0.5 mg / kg qiyaasta labaad ee AMPH . Xilliga birta celceliska celceliska (SE) ee wajiga hore ee duritaanka ee koowaad iyo labaad 0.5 mg / kg kalfadhiyada imtixaanka AMPH waxay ahaayeen 757 (41) iyo 974 (59).
Mishiinka laf-dhabarka kadib. Koox 5 2 0.5 Xulashada ANOVA ee jawaab celinta gulukooska ee 5 mg / kg AMPH ka hor iyo ka dib markii xaddiga XNUMX-dose dareensiiyay saameyn weyn oo ah Kulanka, F(1, 35) = 76.05, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <1.10, p > 0.37. Jaantus Jaantus55 waxay muujineysaa dhibcooyinka celceliska koox kasta iyo cashar.
Shaxanka ayaa muujinaya in saamaynta fadhiga ay ku lug leedahay korodh weyn oo ah jimicsiga caadiga ah (SE) fasaxyada 90 min dufanka 0.5 mg / kg 1, 3674 (216) ilaa 0.5 mg / kg qaddar 2, 6123 (275). Jiritaanka isdhexgalka ama saameynta kooxdu waxay soo jeedisay in dareenka AMPH aysan ku kalsoonayn kooxaha oo dhan. Inkasta oo aysan jirin wax saameyn ah oo saameyn kooxeed oo ku saabsan ANOVA, kormeerka shaxda ayaa muujinaya in kooxda 50 ay soo bandhigtay jawaabta ugu weyn ee horay u ah xaddiga koobaad ee koowaad iyo labaad ee 0.5 mg / kg. Isbarbardhiga la qorsheeyay ee jawaab-celinta ugu horeysay ee 0.5 mg / kg ayaa muujinaysa faraqa u dhaxeeya kooxda 50 iyo kooxda 0 ama kooxda 100, t's(35) <0.48, p > 0.50. Si kastaba ha noqotee, ka jawaab celinta labaad (dareenka kadib) 0.5 mg / kg qiyaasta, kooxda 50 waxay soo bandhigeen dhaqdhaqaaq aad uga weyn kan kooxda 0, t(35) = 2.00, p <0.05, iyo sidoo kale kooxda 100, t(35) = 3.29, p <0.01.
Marka la eego farqiga udhexeeya kooxaha istiraatiijiga ah ee xakameynta pre-injirta ee xiga labaad ee 0.5 mg / kg AMPH oo kor lagu soo sheegay, kor-u-qaad 5 Xusan 2 fadhiga ANCOVA ee jawaabta locomotor ee 0.5 mg / kg AMPH ayaa la sameeyay, xakameynta cirbadeynta ee fadhiga labaad. Falanqaynta Tani waxay keentay saameyn weyn oo ah dareenka, F(1, 34) = 8.65, p = 0.006, saameynta ugu weyn ee fadhiga F(1, 34) = 10.83, p = 0.002, iyo saameyn kale oo muhiim ah, F(4, 34) <0.85, p > 0.50. Muhiimad ahaan, isbarbardhigga qorshaysan ee ku saleysan qaladka MS iyo qaladka df ee ka imanaya ANCOVA ayaa xaqiijiyay in macnaheedu yahay ka jawaab celinta tareenka ee qiyaasta labaad ee 0.5 mg / kg ee AMPH ayaa si aad ah uga weyneyd kooxda 50 marka loo eego kooxda 100, t(34) = 3.09, p <0.01, iyo koox 0, t(34) = 1.88, p <0.05 (hal-dabo), markii isbeddelka hore ee mudista ee kalfadhiga 2 la xakameeyay. Sidaa darteed, kooxda 50 waxay muujiyeen jawaab celin weyn oo dareen-celin kadib markii loo eego 0.5 mg / kg AMPH marka loo eego kooxdii 100 ama koox 0, iyo kala duwanaanshaha kooxdan laguma dhexdhexaadin dhaqdhaqaaq horay loo duray maalmaha imtixaanka.
Saameynta 1.0 mg / kg AMPH.
Maqnaanshaha hore ee cirbadeynta. 5 Group 5 Kulanka 30 ANOVA ee 1-min dhibcaha hore ee cirbadaha loogu talagalay XNUMX mg / kg AMPH xasaasiyadeedka ayaa keenay natiijada ugu weyn ee Kulanka, F(4, 140) = 16.70, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <0.94, p > 0.45. Isbarbardhigga qorshaysan ma helin farqi weyn oo ku saabsan dhaqdhaqaaqa hore ee duritaanka u dhexeeya kooxda 50 iyo kooxda 0 ama koox 100 fadhigii ugu horreeyay, t(175) <1.66, p > 0.10. Si kastaba ha noqotee, fadhigii ugu dambeeyay, kooxda 50 (1167; 140) waxay muujiyeen jajab aad u badan (M; SE) marka loo eego kooxdii 100 (1000; 99), t(175) = 2.35, p <0.05, laakiin kama duwana kooxda 0 (1085, 120), t(175) <1.16, p > 0.20. Sidaa darteed, kala duwanaanta dhaqdhaqaaqa kahortaga kahor ayaa gacan ka gaysatay farqiga u dhexeeya kooxaha 50 iyo 100 jawaab celinta tareenka ee ugu dambeeya 1 mg / kg AMPH dose. Qiyaasta (SE) guud ahaan jajabka jajabka muunada inta lagu jiro wajiga hore ee duritaanka ee Kalfadhiyada 1 illaa 5 waxay ahaayeen: 810 (46), 784 (52), 760 (53), 726 (46), 1009 (51).
Mishiinka laf-dhabarka kadib. Kooxda 5 5 Xulashada ANOVA ee jawaabaha 1 mg / kg AMPH waxay soo saartay saameyn weyn oo muhiim ah oo ah Kulanka, F(4, 140) = 6.72, p <0.001, koox yar - isdhexgalka kalfadhiga, F(16, 140) = 1.57, p = 0.085, oo saameyn kuma leh kooxda, F(4, 35) <0.44, p > 0.77. Falanqaynta isbeddelka Polynomial waxay muujisay isbeddel toosan oo toosan, F(1, 35) = 9.19, p = 0.005, iyo isbedel dhir, F(1, 35) = 21.63, p <0.001, in ka badan fadhiyada 1 illaa 5. Jaantus Jaantus66 waxay muujineysaa dhibcaha celceliska heerka maskaxda ee kooxda iyo koox kasta.
Shaxanka ayaa muujinaya in saamaynta fadhiga ay muujinayso korodh weyn oo dhexdhexaad ah (SE) jimicsiga guud ee tijaabada buuxa ee ka socota 1, 4624 (213) si ay u qabtaan 5, 5736 (272), oo xaqiijinaya soo-jeedinta xasaasiyadda AMPH. Heerka yaryar ee loo yaqaan "Maxima" oo ku saabsan kulamada 1, 3, iyo 5, oo leh qalab kulanno 2 iyo 4, gaar ahaan kooxaha 0 iyo 50. Xubnaha ayaa sidoo kale muujinaya, inkasta oo ayan jirin wada-shaqayn dhexmarta, kooxda 25 waxay soo bandhigtay jawaab celin xoojin ah oo ka soo baxa kulanno oo ay si wayn uga duwan yihiin kooxaha kale ee 4 iyo 5 (9 iyo 22% ka sarreeya, marka loo eego kooxda ugu sarreysa). Isbarbardhiga la qorsheeyay ayaa lagu ogaaday in kooxda 50 aysan si weyn uga duwaneyn kooxaha 0 ama 100, t(175) <0.89, p > 0.40 marka koowaad ama ugu dambeysa 1 mg / kg imtixaanka AMPH.
Xakamaynta isbeddelka sanka sanka ee wax ka qabashada tababarka sukrose
Laba 5 Group 2 Kulanka 0.5 ee ANCOVAs ee jawaab celinta locomotor ee XNUMX mg / kg AMPH ka hor iyo ka dib markii habka xasaasiga ah, oo ay ku jiraan sanka oo dhan sanadka inta lagu jiro tababarka sukrose ee CS joogta iyo CS oo maqnaanshaha sida kala-duwan oo kala duwan, ma helin saameyn muhiim ah labada nooc, F(1, 18) <1.03, p > 0.31. Sidaa darteed, habka looga jawaabayo inta lagu jiro tababarka ma uusan dhexdhexaadin kala duwanaanshaha kooxda ee ka jawaab celinta 0.5 mg / kg AMPH.
Laba 5 Group 5 Kulanka 1 ee ANCOVAs ee jawaab celinta locomotor ee XNUMX mg / kg inta lagu jiro fadhiyada xasaasiga ah ee leh sanka oo dhan sanadka (CS joogta, CS maqnaanshaha) sida kala duwanaansho goonida ah wax saameyn ah u lahayn saameynta saameynta gorgortanka halka CS-ta ay joogeen, F(4, 104) <1.04, p > 0.38, iyo saameynta ugu yar ee isweydaarsiga halka CS uu maqnaa, F(1, 18) = 3.32, p = 0.085.
Dood
Natiijooyinka daraasadani si joogta ah uma taageersanayn aragtida kooxdan 50 waxay muujineysaa jawaab celin dheeri ah oo ka soo baxda fadhiyada marka loo eego kooxaha kale. Macluumaadka 1 mg / kg AMPH ayaa xaqiijiyay soo bixitaanka dareen-celinta iyadoo la adeegsanayo habka daaweynta ee kale. Tilmaamayaasha kooxaha oo dhan waxay muujinayaan isbeddel ballaadhan inta lagu jiro kalfadhiyada dambe ee kooxda 25, oo aan lahayn caddaynta noocaas ah ee 50. Taas bedelkeeda, natiijooyinka 0.5 mg / kg ayaa muujinaya isbeddellada ugu weyn ee kooxda 50, isla mar ahaantaana ay xaqiijinayso kororka guud ee jawaab celinta locomotor ee kooxaha kooxaha ilaa labaad iyo xaddiga ugu horeeya ee 0.5 mg / kg AMPH. Saameynta nullaxa ee cirbadeynta salineed ayaa xaqiijiyay in fekerka ama cadaadiska la xidhiidha cirridka aan wax saameyn ah ku lahayn saameynta AMPH.
Xogta sanka ayaa mar kale shaaca ka qaaday koror guud oo ku saabsan habka looga jawaabayo inta lagu gudajiro fadhiyada tababarka marka CS uu joogo, iyadoo aysan jirin wax isbarbar dhig ah oo ku saabsan goorta CS uu maqnaa. Sidaa darteed, xayawaanku waxay u muuqdeen inay helaan xiriirka ka dhexeeya CS iyo rajada ah abaalmarinta guusha. Kala duwanaanshaha kooxda ee inta jeer ee sanka-qaadashada sanka markii CS lagu soo bandhigayey si ku-meel-gaar ah inta jeer ee bixinta abaalmarinta iyada oo loo eegayo jadwalka, iyadoo kooxaha 75 iyo 100 ay soo bandhigaan buqshadaha sanka ugu badan, kooxda 50 waxay soo bandhigeen lambarro dhexdhexaad ah oo kaadhadhka sanka ah, iyo kooxaha 0 iyo 25 oo soo bandhigaya calaacalaha sanka ugu yar. Natiijooyinkaani waxay soo jeedinayaan in CS ay u maamusho habka wax ka qabashada iyadoo la raacayo suurtagalnimada guud ee abaalmarinta. In kasta oo la qiyaasi karo, hal sharrax oo suurtagal ah oo loogu talagalay heerarka sanka hoose ee saamiga leh CS oo jooga kooxda 50 ee tijaabada 2 vs. tijaabada 1 ayaa laga yaabaa inay tahay soo gaabintii muddada dhexdhexaadinta, iyadoo muddooyinka muddada dheer ee tijaabada (tijaabada 1) ay u muuqdaan inay dhiirigelinayaan dhiirigelin u janjeeraha tanna waxay la xiriirtaa kororka isbedelka ee DA oo kujira murugada gudaha, prelimbic iyo shuruudaha infralimbic (Dalley et al., 2002). Sidaa daraadeed, 30% hoos udhigista dhexdhexaadinta isdhexgalka ee tijaabada ah 2 (iyo 3) ayaa laga yaabaa inay bedeleen Qiyaasta DA-da oo waxay kor u qaadeen doorashooyin dheeraad ah (sida, hagida jimicsiga) ka jawaabida kooxda 50 inta lagu jiro tijaabooyinka tababarka ee tijaabada 2 marka loo barbar dhigo tijaabada 1.
Dhibaatooyinka weyn ee saameyn ku yeeshay saamaynta isbedelka sanka ee sanka ku yaalla CS gudaheeda ayaa muujinaya in habka wax looga qabanayo tababbarrada sukrose aysan dhexdhexaadin saameynaha jadwalka CS-sukrose kala duwan jawaabaha AMPH. Waxyaabaha ugu muhiimsan ee saameyn ku yeelanaya xaaladaha maqnaanshaha CS ee ANCOVA ee jawaabaha locomotor ee 1 mg / kg AMPH waxay soo jeedinaysaa in rabitaanka uur-qaadida aan-lahaanshaha-bilaashka ah ay sharaxday qaar ka mid ah isbeddelka saameynta saameynta saameynta AMPH inta lagu jiro kalfadhiyada xasaasiga ah.
Si wadajir ah, caddaynta waxay muujineysaa in saameynta taariikhda qaboojinta ay noqon karto mid la fahmi karo 0.5 AMPH marka loo eego 1 mg / kg AMPH, iyo in nidaam keena dareen-celinta haddii maqnaansho kale oo wax lagu macaamilayo ay been-abuureyso ama wax ka qaban karto saamaynta saamaynta Dareen-dhexdhexaadinta dhiirrigelinta dabeecadda (ie, abaal-marinta isbeddel joogto ah).
Dareenka dabeecadda AMPH waa saameyn adag sheybaarka. Si kastaba ha noqotee, ka baxsan sheybaarka, kaliya tiro yar oo ah shakhsiyaadka khamaarka si joogto ah ugu sii kordhaya heerarka cudurada. In kasta oo halista dareenka ay la xiriirto halista balwadda (ama raadinta maandooriyaha), gaar ahaan cilmi nafsiga (Vezina, 2004; Flagel et al., 2008), arrimo badan oo ka baxsan khatarta xasaasiga ayaa laga yaabaa inay u horseedaan mid inuu ku noqdo balwad (tusaale ahaan, Verdejo-Garcia et al., 2008; Conversano et al., 2012; Volkow et al., 2012). Si kastaba ha ahaatee, qodobada ku habboon ee keena nuglaanshaha dareenka ayaa laga yaabaa inay la falgalaan taariikhda qaboobaha si ay u muujiyaan saameynta abaalmarinta aan la saadaalin Karin (ie, 50% CS-US schedule) oo ku saabsan fal-dambiyeedka DA. Si loo baaro suurtogalnimada, tijaabinta 3 waxay ku shaqeeysatay habka isku midka ah ee tijaabada 2 laakiin waxay isticmaaleen Lewis strain halkii jiirka jilicsan ee Sprague Dawley.
Sprague Dawley jiirka ayaa soo bandhigaya heerar dhexdhexaad ah oo gaadiidleyda DA, oo leh heerar ka hooseeya jiirka Wistar strain (Zamudio et al., 2005), laakiin heerar ka sareeya kahaadhka Wistar-Kyoto ("walax" u eg ') oo ku taal unugyada loo yaqaan' Nucleus accumbens ', amygdala, aagga ventral tegmental iyo buundada nigra (Jiao et al., 2003). Astaantan ayaa laga yaabaa inay ku siiso Sprague Dawley jiirka oo keliya dhexdhexaad xasaasi ah u ah khalkhalgelinta deegaanka ama dawooyinka ee DA. Taas bedelkeeda, jiirka Lewis wuxuu soo bandhigayaa heerar hoose oo gaadiidleyda DA sidoo kale D2 iyo D3 DA qaatayaasha ku jira qulqulka Nucleus-ka iyo xirmooyinka marinka marka loo eego noocyada kale (tusaale ahaan, F344) (Flores et al., 1998). Kala duwanaanshahan qaabdhismeedku wuxuu gacan ka geysan karaa jawaabta kaladuwan ee Lewis ee ku saabsan wax ka qabashada DA. Jiirka Lewis sidoo kale waxay soo bandhigaan jawaabo kaladuwan oo laxiriira maareynta daroogada tijaabada ah marka loo eego noocyada kale (tusaale, F344). Tan ugu muhiimsan, jiirka Lewis waxay u muujiyaan dareen weyn methamphetamine, oo lagu garto jawaab celin hooseysa ee qiyaasaha hore laakiin jawaabta sare ee qiyaasaha dambe (Camp et al., 1994). Jiirka Lewis sidoo kale waxay soo bandhigaan feejignaan dheeri ah oo ah taabashada xaddiga kookaha (Kosten et al., 1994; Haile et al., 2001). Iyadoo lagu saleynayo qaabka saameyntan, waxaanu ku qanacsanahay in jiirarka Lewis ay noo suurtageli karto in aan baarno haddii ay u nugul yihiin dareenka sareeya ee saameynta jadwalka cabbirka ee jawaabaha dambe ee AMPH.
tijaabi 3
Qalabka iyo hababka
Nidaamka ayaa ahaa mid la mid ah tijaabadii 2, oo laga soo qaatay isticmaalka Lewis Jaadka (200-225 marka la yimaado, Charles River, Quebec, Canada).
Natiijooyinka
Sigaarka sanka inta lagu jiro kalfadhiyada qaboojinta sukrose
5 Group x XUMADA 15 2 Heerka XNUMX (CS joogta, CS maqnaanshaha) ANOVA ee sanka sanka ayaa keenay saameyn weyn oo muhiim ah ee Kooxda, F(4, 34) = 6.12, p = 0.001, Kulanka, F(14, 476) = 3.42, p <0.001, iyo Wajiga, F(1, 34) = 20.83, p <0.001, iyo sidoo kale is-dhexgal muhiim ah oo saddex geesood ah, F(56, 476) = 1.56, p = 0.008. Guddiyada (A, B) Jaantuska Jaantus77 qorshee dhibcaha dhibcaha sanka ee kooxaha CS iyo wejiyada maqnaanshaha CS, siday u kala horreeyaan. Isbarbardhiga labada dhinac waxay muujineysaa in saameynta ugu weyn ee Wajiga ay ka muuqato guud ahaan jawaabaha sanka ee sanduuqa markii CS la joogo iyo maqnaanshaha. Sidaa darteed, jawaabaha cunnada ayaa si aad ah uga dhacay inta badan jawaabihii horay u bislaaday. Saamaynta ugu weyn ee Kooxda iyo Fadhiga si sahal ah looma fasirin sababtoo ah isdhexgalka amarka sare. Isdhexgalka seddex-geesoodka ah ayaa ka tarjumayay isugeynta dhibcaha shanta koox heer deggan oo deggan marka loo eego kal-fadhiyada markii CS maqnaa [Guddi (B)], oo ay weheliyaan kala duwanaansho dhibcood marka CS-du ay soo bandhigtay nuucyo khafiif ah oo koox kasta ah oo isku mid ah nidaamka darajada jimicsiga: laga bilaabo ugu sarreeya (koox 100) ilaa hoose (koox 25) [Guddi (A)]. Kaliya isbeddel toos ah ee isdhexgalka ayaa ahaa mid muhiim ah, F(4, 34) = 4.03, p = 0.009, oo ka tarjumaysa kororka joogtada ah ee sanka ka soo baxa kulamada kooxaha 100 marka CS-du joogtey oo ka soo horjeeda isbedel aan fiicneyn oo kordhinaya sanka sanka ee kooxo kale inta lagu guda jiro marxaladan.
Hab-socodsiinta sanduuqyada cirifoorka
Kooxda 5 3 ANOVA ayaa saameyn weyn ku yeeshay Kulanka, F(2, 70) = 23.07, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(8, 70) <1.47, p > 0.18. Nidaamka curvilinear ee celceliska (SE) dhibcaha socodka ayaa ka soo baxay kalfadhigii 1, 1076 (74), illaa iyo fadhigii 2, 644 (48), ilaa kalfadhigii 3, 762 (59). Isbarbardhiga la qorsheeyay ee kooxda 50 ee kooxda 0 iyo kooxda 100 ee ku saabsan kulamada ugu horeeya uguna dambeeya ee laqabsashada ayaa muujiyay in si aad ah ay uga yar yihiin jajabka dogobka kooxda 50 (M = 911; SE = 109) iyo kooxda 0 (M = 1103; SE = 176) fadhiga habeynta 1, t(105) = 2.02, p <0.05, laakiin farqi uma dhaxeeyo kooxda 50 iyo kooxda 100 (M = 1066; SE = 150), t(105) <1.20, p > 0.20, kulankaan. Kooxda 50 si weyn ugama duwanaan labada koox 0 ama koox 100 fadhigii ugu dambeeyay ee habeynta, t(105) <0.93, p > 0.30. Sidaa darteed, celceliska jawaab celinta tareenka ee daroogada ee kooxaha muhiimka ah kuma aysan kala duwanaan si joogto ah baaritaanka ka hor.
Kulanno tijaabo ah
Saline. Kooxda 5 2 XNUMX Kulanka ANOVA ee jawaabaha locomotor ee fadhiga ugu dambeeya ee habitinta iyo casharka salineinka saline wuxuu soo saaray saameyn weyn oo muhiim ah ee Kulanka, F(1, 35) = 50.12, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <0.57, p > 0.68. Jaantus Jaantus88 waxay muujinaysaa dhibcaha kooxood ee labada xisadood waxayna tilmaamayaan in saamaynta fadhiga ay muujinayso hoos u dhac weyn oo ka yimaada hab-nololeedka iyo tijaabada. Sidaa darteed, helitaanka cirbadda per se (tus., rajada, walbahaarka) ma wanaajin wax jawaab celin ah.
Saameynta 0.5 mg / kg AMPH.
Maqnaanshaha hore ee cirbadeynta. Kooxda 5 2 Xulashada ANOVA ee ka hortagidda mudista horteeda waxay keentay saameyn weyn oo muhiim ah oo ah Kulanku, F(1, 35) = 15.04, p <0.001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <1.19, p > 0.33. Isbarbardhigga qorsheysan ma helin farqi weyn oo u dhexeeya kooxda 50 iyo kooxda 0 ama koox 100 midkood labada kulan ee imtixaanka, t(70) <0.99, p > 0.30. Sidaa darteed, kala duwanaanshaha aasaasiga ah ee dhaqdhaqaaqa kahortaga kahor ma uusan xisaabin kala duwanaanshaha kooxeed ee jawaab celinta tareenka ilaa 0.5 mg / kg AMPH. Kalsoonida (SE) jabka beam ee wajiga hore ee duritaanka ee koowaad iyo labaad (dareenka kadib) fadhiyada 0.5 mg / kg waxay ahaayeen 325 (25) iyo 473 (36).
Mishiinka laf-dhabarka kadib. 5 Group 2 Kulanka 0.5 ANOVA ee jawaab celinta locomotor ee 1 mg / kg qiyaaso la bixiyay ka hor iyo ka dib XNUMX mg / kg AMPH oo saameyn weyn ku yeeshay Casharka, F(1, 34) = 87.44, p <0.0001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 34) <0.94, p > 0.45. Jaantus Jaantus99 ayaa muujinaya dhibcaha celceliska celomotorka ee koox kasta iyo kalfadhiiba, waxayna muujineysaa in Saameynta Kulanku ay muujinayso jawaabta guud ee jawaabta labaad ee 0.5 mg / kg, oo la socota dareenka. Shaxanku wuxuu sidoo kale muujinayaa in kooxdu ay si aad ah isku mid ah uga sameysey 1, laakiin kooxdan 50 waxay soo bandhigtay dhaqdhaqaaqa xeeladeysan oo ka badan kooxaha kale ee 2. Isbarbardhiga la qorsheeyey ee jawaabta ugu horeysay ee 0.5 mg / kg qiyaasta ma muujin farqi weyn oo udhaxeeya kooxda 50 iyo kooxda 0 ama kooxda 100, t(35) <1.28, p > 0.20. Si kastaba ha noqotee, kooxda 50 waxay muujiyeen jawaab celin aad u weyn oo tareenka ah oo ku socota qiyaasta labaad ee 0.5 mg / kg marka loo eego kooxdii 0, t(35) = 4.32, p <0.001, ama koox 100, t(35) = 2.24, p <0.05.
Saameynta 1 mg / kg AMPH.
Maqnaanshaha hore ee cirbadeynta. Kooxda 5 × 5 Kalfadhiga ANOVA ee 30-min dhibcaha hordhaca ah ee kulamada xasaasiga ah waxay soo saareen saameyn weyn oo kulanka, F(4, 140) = 4.10, p = 0.004, iyo saameyn kale oo muhiim ah, F(4, 35) = 1.25, p > 0.31. Isbarbardhiga la qorsheeyay ayaa lagu ogaaday in jajabka dogobku inta lagu jiro wajiga hore ee mudista (M; SE) ay aad uga hooseeyeen kooxda 50 (395; 62) marka loo eego kooxda 100 (508; 62), t(175) = 2.58, p <0.01, laakiin ma aha koox 0, t(175) <1.83, p > 0.10, 1 mg / kg AMPH session 1. Kulankii 1 mg / kg ee AMPH ee ugu dambeeyay, isbarbardhiga la qorsheeyay ayaa sidoo kale lagu ogaaday in dhaq dhaqaaqa kahortaga hore ee kooxda 50 (378; 60) uu aad uga hooseeyo kooxda 100 (650; 75 ), t(175) = 6.17, p <0.001, laakiin kuma jirin kooxda 0, t(175) <1.84, p > 0.10. Maaddaama jihada kala duwanaanshaha kooxdan (kooxda xakamaynta = kooxda 50) ay ka soo horjeedday qaabka la qiyaasay, kala duwanaanshaha kooxeed ee dhaqdhaqaaqa ka dambeeya duritaanka ee la jaan qaadaya mala-awaalka looma nisbeyn karo kala-duwanaanshaha aasaasiga ee kahortagga hore. Micnaha (SE) guud ahaan jajabka beam inta lagu gudajiray wajiga hore ee duritaanka ee Kalfadhiyada 1 illaa 5 waxay ahaayeen: 442 (34), 452 (32), 542 (40), 411 (26), 504 (37).
Mishiinka laf-dhabarka kadib. Kooxda 5 × 5 fadhiyada ANOVA ee jawaabaha ee qiyaasta 1 mg / kg waxay soo saartay saameyn weyn oo muhiim ah kulanka, F(4, 140) = 6.15, p <0.001, oo aan lahayn saameyn kale oo muhiim ah, F(4, 35) <0.57, p > 0.68. Falanqaynta isbeddelka Polynomial waxay muujisay isbeddel toosan oo toosan, F(1, 35) = 9.34, p = 0.004, iyo isbedel dhir, F(1, 35) = 5.08, p = 0.031, natiijada dambe waxay muujineysaa maxima qaraabo ah fadhiga 3 iyo 5. Jaantus Jaantus1010 shirqoolka ujuuradan waxayna muujineysaa in, in kasta oo ay jirto maqnaansho weyn oo ku dhex jirta ANOVA, kooxda 50 waxay soo bandhigtay gundhig weyn oo ka weyn afarta koox ee kale iyadoo laga jawaabayo xaddiga ugu dambeeya ee 1 mg / kg. Marka loo eego, isbarbardhiga la qorsheeyay ayaa shaaca ka qaaday dhibcaha macnaha weyn ee kalfadhiga 5 ee kooxda 50 marka loo eego dhamaan kooxaha kale, t(35) > 3.68, p <0.001.
Xakamaynta isbeddelka sanka sanka ee wax ka qabashada tababarka sukrose
Laba 5 Group 2 Kulanka 0.5 ee ANCOVAs ee jawaab celinta locomotor ee XNUMX mg / kg AMPH ka hor iyo ka dib markii habka xasaasiga ah, oo ay ku jiraan sanka oo dhan sanadka inta lagu jiro tababarka sukrose ee CS joogta iyo CS oo maqnaanshaha sida kala-duwan oo kala duwan, ma helin saameyn muhiim ah labada nooc, F(1, 32) <0.44 p > 0.51. Laba 5 Kooxda × 5 Kalfadhiga ANCOVAs ee jawaab celinta tareenka ee 1 mg / kg AMPH inta lagu gudajiray kal-fadhiyada xasaasiga ah ee wadarta sanka sanka (CS xaadirka, maqnaanshaha CS) maadaama kaladuwanaansho kaladuwan aysan keenin wax saameyn ah oo muhiim ah oo ku saabsan isweydaarsiga halka CS uu joogay ama maqnaa, F(1, 33) <0.14, p > 0.71. Sidaa darteed, habka ka-jawaab-celinta daroogada ma uusan xisaabin kala duwanaanshaha kooxeed ee jawaabaha tareenka ee qiyaas kasta oo ah AMPH.
Dood
Dareenka dareenka ayaa loo sameeyay saameynta soo noqnoqda 1.0 mg / kg amphetamine. Habdhaqanka iyo xogta cusbada ayaa xaqiijinaya in saameyntani aysan aheyn kala duwanaansho hore u jiray, rajada, ama jawaabaha la xiriira walbahaarka ee duritaanka. ANCOVAs oo leh sanka oogada ayaa xaqiijinaya in saameyntani aysan aheyn habdhaqanka daroogada aan xorta aheyn. Xogta sanka ayaa lafteeda muujisay in kooxaha ay heleen xiriirka ka dhexeeya CS iyo rajada abaalmarinta sukrose. Heerarka darajo kooxeed ee sanka-poke ee ka jawaabaya dhamaadka tababarka ayaa iswaafajiyay guud ahaan inta jeer ee abaalmarinta ee ka hooseeya jadwalka kala duwan ee ugu sareeya (kooxda 100) ilaa kan ugu hooseeya (kooxda 0), sidii ay ku sameysay tijaabada 2. celceliska guud ee hooseeya heerarka sanka ee tijaabadan marka la barbar dhigo tijaabooyinka 1 iyo 2 ayaa laga yaabaa inay ka tarjumaan habab xulasho leh oo ka jawaabaya tilmaamaha abaalmarinta jiirka Lewis (Kosten et al., 2007).
Xogta qiyaasta 0.5 mg / kg waxay muujisay in jawaabta bilowga hore ee AMPH ee jiirka Lewis (Jaantus (Figure9) 9) waxoogaa waa la xakameeyay marka loo eego Sprague Dawley jiirka (tijaabada 2; Sawirka Sawirka5), 5), laakiin kororka ka dhex jira kooxda ee jawaabta qiyaasta labaad ee jiirka Lewis aad ayuu u badnaa (ku dhawaad labanlaab jawaabta xNUMX mg / kg qiyaasta) ka dib markii loo fiirsaday 0.5-fadhiga AMPH-ga ee sida qaalibka ah, kooxda 5 waxay soo bandhigtay jawaab celin aad u weyn. marka loo eego kooxaha oo dhan marka laga reebo kooxda 50 ilaa ta labaad (ie, ka-dib-u-feejignaan) 25 mg / kg AMPH qiyaasta iyo jawaab-celinta ka weyn tan kooxaha kale oo dhan, oo ay ku jiraan kooxda 0.5, illaa xNUMX mg / kg AMPH ee ugu dambeeya xaddiga xasaasiga ah) .
Falanqaynta oo kooban oo ku saabsan darajooyinka kooxda ee tijaabooyinka
Si loo go'aamiyo isku halaynta kala duwanaanshaha kooxda ee dareenka, falanqaynta aan xuduuda lahayn waxay qiimeeysay isku dhaca u dhexeeya kooxda iyo darajada celceliska jawaab celinta jawaabta labaad (ka dambeysa AMPH) 0.5 mg / kg qiyaasta iyo xNUMX mg / kg ee ugu dambeeya ee qiyaasta AMPH laga bilaabo tijaabooyinka 1.0. Falanqayntaasi waxay soo saartay saameyn laxaad leh, ![[var phi]](http://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcents/x03C6.gif){kind=small}
= 0.986, p = 0.025, oo ka tarjumeysa xaqiiqda ah in kooxda 50 ay kaalinta koowaad ka gashay dhammaan laakiin aan isbarbar dhig ku sameyn. Darajada sare ee kooxda 50 marka la barbar dhigo dhammaan kooxaha kale ee ka jawaabaya tan labaad (AMPH post-daba-dheer) 0.5 mg / kg qiyaasta waxaa lagu muujiyey Jaantuska Jaantus55 (Tijaabada 2) iyo Jaantus Jaantus99 (tijaabi 3). Darajada sare ee kooxda '50' marka loo eego kooxaha kale ee ka jawaabaya xaddiga ugu dambeeya ee 1.0 mg / kg waxaa lagu muujiyey Jaantuska Jaantus22 (Tijaabada 1) iyo Jaantus Jaantus1010 (tijaabi 3). Waxa kaliya ee ka reebban qaabkani wuxuu ahaa jawaabta cabirkii ugu dambeeyay ee 1.0 mg / kg ee jiirka Sprague-Dawley ee tijaabada 2.
Dood guud
Tijaabada taxanaha ah ee tijaabada ah waxay tijaabisay mala awaalka ah in soo-gaadhista joogtada ah ee jadwalka-khamaarka abaalgudka ah ay u dareensiin karto maskaxda wadooyinka sida aadka u badan soo-gaadhista daroogada ee xadgudubka. Caddaynta saamayntan oo kale waxay soo jeedinaysaa in neuroplasticity, oo loo malaynayo isla fikirka inay gacan ka geysato balwadda maandooriyaha, waxaa sababi kara soo-gaadhis joogto ah oo loogu talagalay jadwalka abaalmarinta aan la saadaalin karin. Iyada oo la raacayo suugaanta ku saabsan qabatinka maandooriyaha, jaangooyada hoose ee jawaabta 0.5 iyo 1.0 mg / kg ee qiyaasta falcelinta nidaamka AMPH, oo leh dhaqdhaqaaq weyn ka jawaab celinta qaddarka dambe ee hawlgalka qeexaya dareenka (Robinson iyo Berridge, 1993; Piired iyo Kalivas, 1997; Vanderschuren iyo Kalivas, 2000).
Guud ahaan, natiijooyinka waxay la jaan qaadayaan aragtidayada. Si kastaba ha noqotee, waxay sidoo kale tilmaamayaan kala duwanaansho aad u weyn oo saameynnada tijaabada ah sababao la xiriira arrimaha. Saamaynta jadwalka qaboojintu waxay ahaayeen kuwo dhexdhexaad ah laakiin isdaba joog ah, iyadoo kooxda 50 ay muujineyso jawaab celin ka weyn afarta koox ee kale labada daawo qaadasho ee soo socota shanta daawo-qaadashada. In kasta oo guud ahaan FQiimaynta saamaynta kooxda la xiriirta ee falanqaynta kaladuwanaashaha badanaa inta badan ma ahan kuwa muhiim ah, kala duwanaanshaha kooxda muhiimka ah waxaa lagu xaqiijiyay isbarbardhiga qorsheysan ee labada dhinac ah. Marka tan la eego waa in la ogaadaa in, “Fikirka hadda jira, si kastaba ha ahaatee, waa muhiimadda guud ee loogu talagalay [ F gudaha ANOVA] qasab ma ahan. Ugu horreyntii, fikradaha lagu tijaabiyay imtixaanka guud iyo tijaabinta isbarbardhiga ayaa aad u kala duwan, oo leh heerar aad u kala duwan oo awood ah. Tusaale ahaan, guud ahaan F dhab ahaantii waxay u qaybisaa kala duwanaanshaha kooxaha ka mid ah tirada heerarka xornimada ee kooxaha. Tani waxay leedahay saameynta dilidda guud ahaan F Xaaladda ay ku jiraan dhowr koox macnahoodu way isleegyihiin laakiin way ka duwan yihiin macnaha kale ”(Howell, 1992, p. 338). Tani waa sida saxda ah ee xaaladda lagu dabaqi jiray tijaabooyinka hadda jira, halkaas oo kooxda 50 laga filaayey inay ku kala duwanaato kooxda 0 iyo kooxda xakamaynta 100 laakiin wax farqi ah oo u dhexeeya kooxahan xakamaynta ah lama saadaalin kooxda 25 ama kooxda 75.
Xogta sanka ayaa cadeeyay in, tijaabo kasta, xayawaanku ay heleen xiriirka ka dhexeeya CS iyo rajada laga qabo in lagu guuleysto abaalmarinta. Xidhiidhka ka dhexeeya inta jeer ee xajmiga sanka ee kooxaha kala duwan iyo guud ahaan abaalmarinta abaalmarinta iyada oo loo eegayo jadwalka tababarkooda ayaa soo jeedinaya in celcelis ahaan celceliska celcelis ahaan abaalmarinta hannaan maandooriyaha ka madaxbannaan yahay. Si kastaba ha noqotee, la'aanta saameynta dhexdhexaadinta ee sanka ka imanaya jawaabaha la xiriira kooxda ee jawaabta AMPH ee ANCOVAs ayaa muujisay in habraacyo kaladuwan ay hoosta ka galaan labada dabeecadood.
Xaaladaha qaarkood, saamaynta jadwalka qaboojintu waxay ahayd mid cad iyadoo laga jawaabayo qiyaasta AMPH ee ugu horreysa; Xaaladaha kale waxay ka soo baxday oo keliya ka dib qaadashooyinka soo noqnoqda. Kala duwanaanshaha kooxda ee jawaabta jaangooyada qiyaasta AMPH ee ugu horreysa waxay soo jeedineysaa in soo-gaadhista jadwalka abaal-marinta khamaarka ay ku filan tahay kali kicinta dareenka. Kala duwanaanshaha kooxda ee isu socodka ka dib qiyaaso badan oo AMPH ah ayaa muujinaya saameyn dheeri ah oo lagu tilmaami karo “nuglaanta,” taas oo la soo bandhigo oo keliya marka lagu daro soo-gaadhista joogtada ah ee wakaaladda dareenka aasaasiga ah (tusaale, amphetamine).
Farqiga u dhexeeya qaabka jawaab celinta guud ahaan tijaabooyinka ayaa soo jeedinaya in muddo dheeri ah oo udhaxeysa tababarka iyo bilowga AMPH bilowga ah ay kor u qaadi karto fursadda lagu ogaanayo saameynta dareenka ee dareenka daaweynta. Tani waxay sidoo kale soo jeedineysaa in saameynta saameynta abaalmarinta sharuuddu ay ku imaan karto waqti ka dib, ifafaale sidoo kale lagu arkay dareenka kicinta (Grimm et al., 2006). Qaabka jawaab celinta labada qiyaasood ee amphetamine wuxuu soo jeedinayaa in qiyaasta 0.5 mg / kg laga yaabo inay wax ku ool u noqoto muujinta saameynta taariikhda xaalad. Tani waxay sidoo kale soo jeedineysaa in saameynta qaboobaha ee habka borotokoolka hadda lagu jiro ay yihiin waxoogaa khiyaano ah oo laga yaabo inay isku buuqdo saameynta saqafka iyadoo la adeegsanayo qiyaasta AMPH iyo xaaladaha dhalinaya de novo dareenka.
Tijaabada 3, qaabdhismeedka biphasic ee jawaab celinta xNUMX mg / kg qiyaasta iyo soo ifbaxa horusocod ah oo ka sarreeya kooxda '0.5' wuxuu la mid yahay astaantii laga filaayay jiirka Lewis ee ka jawaabaya methamphetamine (Camp et al., 1994). Tani waxay taageereysaa ansaxnimada natiijooyinka hada jira waxayna soo jeedineysaa isugeyn dhexmarta waxyaabaha u nugul u nuglaanta u nuglaanshaha dareenka maskaxda iyo jadwalada u eg abaalmarinta abaalmarinta.
Tijaabooyinka guud, jawaabta ka dambeysa dareenka ee kooxda 50 guud ahaan way ka sarreysay tan kooxaha kale iyadoo la adeegsanayo qiyaaso kala duwan oo amphetamine ah iyo noocyo kala duwan oo xayawaan ah. Si kastaba ha noqotee, kala-duwanaanta sare ee kooxda dhexdeeda iyo dheellitirka u dhexeeya cabbirka saamaynta kooxda waxay muujineysaa door arrimo kale ee nidaamka fal-celinta DA ee fal-celinta amphetamine ka dib soo-gaadhista jadwalka kaladuwan ee abaalmarinta lagu guuleysto. In kasta oo jawaabaha DA neurons ay u leeyihiin abaalmarinta calaamadaha ayaa laga yaabaa inay bixiyaan nooc isku-dhafan oo khamaar ah (Fiorillo et al., 2003), sida moodooyinka oo dhan, waxaa jira luminta macluumaadka ujeeddooyinka 'parsimony' - tusaale ahaan, si loo muujiyo hanaan muhiim ah. Natiijo ahaan, qaabka saamaynta dhammaan xaaladaha CS-US ee asalka ah ee Fiorillo et al. Daraasadu si buuxda ugama ay bixinayso jawaabta hoose ee amphetamine. Dib-u-habeyn dheeraad ah ee moodelka waxaa loogu yeeraa inay si buuxda u qabato dhinacyada khamaarka ee saameyn ku leh nidaamka DA.
Isku soo wada duuboo, natiijooyinka taxanahan tijaabooyinka waxay bixiyaan taageero kumeelgaar ah mala awaal ah in soo-gaadhista joogtada ah ee jadwalka-khamaarka abaal marintu ay kor u qaaddo firfircoonida maskaxda ee nidaamka DA oo loo maro caqabad maskaxeed. Sidaasoo kale, waxay kordhiyaan natiijooyinka Singer et al. (2012) oo muujiyey taas, marka loo eego jadwalka go'an, ka hor soo-gaadhista jadwalka xoojinta isbedelka ee qaab hawleed ayaa xoojinaya jawaabta xigta ee amphetamine. Gaar ahaan si gaar ah, natiijooyinka hada jira waxay muujinayaan hubin la'aantan bixinta abaalgudku waa qodobka ugu muhiimsan ee salka ku haya saameynta abaalmarinta doolar. Baaxadda weyn ee saamaynta qalliinka hawlgalka ayaa si weyn uga weyn saamaynta laga helay tijaabooyinka hadda jira. Tani waxay ka tarjumi kartaa soo-gaadhis weyn oo daran oo ku dhaca waxqabadka khamaarka (55 vs. 15 maalmood); waxaa laga yaabaa inay ka tarjumeyso saameynta u baahan jawaab firfircoon si loo helo abaalmarinta (tusaale, doorka hay'ad) halkii ay ka ahayd soo-gaadhsiin dadban, sida ku cad daraasadda hadda jirta. Kordhinta muddada tababarka ee muuqaalka xaadirka ah wuxuu gacan ka geysan doonaa xallinta su'aalahan.
Saxnimada abaalmarinta doorsoomaha iyo jadwalka xoojinta iyadoo moodooyinka khamaarka laga soo qaadan karo tijaabooyinkan. Cilmibaarista mustaqbalka ee baaraysa saameynta xaaladaha xaalad ee taariikhda qatarta qaadashada ee howlaha khamaarka ee feejigan ayaa wax ka qaban kara arrintan. Sidoo kale, xiriirka ka dhexeeya dareenka dabeecadda ee laga helay halkan iyo jawaabta sareysa ee loo yaqaan 'jawaab celin' jawaab celin ah oo ku saabsan amphetamine oo dhowaan laga helay khamaarlayaasha cudurada ku dhaca waa inay sugaan baaritaan dheeri ah (Boileau et al., 2013). Micro-dialysis-ka ayaa ka jawaabi kara su'aashan, saadaasha ku saleysan xogta aadanaha waxay noqon laheyd in sii deynta DA ee kooxda '50' khamaarka fal-galka 'waxaa si muuqata loogu arki karaa go' aanka (sensorimotor) halka laga isticmaali lahaa marinka ventral (limbic) striatum . Xaqiijinta 50% isbedelka CS + abaalmarinta muuqaalka astaamahan kale waxay taageeri doontaa adeeggeeda sida moodada tijaabada ah ee 'PG'.
Halka noocyada khamaarka qaarkood ay si cad u keeneen jawaab qalab (tusaale, mashiinnada ciyaarta), qaababka kale ee khamaarka (tusaale, bakhtiyaa-nasiibka) xiriirka ka dhexeeya ficilka (iibsashada tigidhka, tusaale ahaan, dhigista sharadka), tilmaamaha abaalmarinta (ie. , nambarada bakhtiyaa nasiibka) iyo abaalmarinta lafteeda (lambarka guuleysta iyo bixinta lacagta) ayaa aad u baahsan. Si kastaba ha noqotee, firfircoonida DA inta lagu jiro mudada CS-US ayaa dhici karta inay dhacdo. Tani waxay sharxi kartaa sababta, markii “lambarka guuleysta” la shaaciyo, fiiro gaar ah ayaa loo yeelaa iyadoo kubad bakhtiyaanasiib ah oo shaqsi walba uu isku xigxigayo si loo sameeyo taxanaha gaarka ah ee lambarrada ku guuleysta. In kasta oo suuragalnimada lambar gaar ah oo dhacayaa xisaab ahaan lagu qeexay, natiijada kubbad kasta oo bakhtiyaanasiib ah waa mid laba-cirib ah (u dhiganta lambarka ciyaaryahanka) ama seeg (u dhigma lambarka ciyaaryahanka) - natiijada ka soo baxda tijaabo kasta oo la bixiyo lama yaqaan. Muuqaalka noocan oo kale ah wuxuu si fiican u tilmaami karaa waayo-aragnimada kooxda 50 ee tijaabooyinka hadda jira, halkaas oo abaalmarin lagu siiyay si aan macquul ahayn laakiin sidoo kale aan la saadaalin karin oo CS-da ayaa kaliya muujisay suurtagalnimada abaalmarin iyada oo aan shaaca laga qaadin inay ku dhici doonto maxkamad la siiyay. Qalabka mashiinnada ayaa si xoog leh loola xiriiriyaa PG marka loo eego tikidhada bakhtiyaa-nasiibka (Cox et al., 2000; Bakken et al., 2009), oo muujinaya door muhiim u ah qodobbada aaladda (iyo sida ugu dhaqsaha badan) ee abaalgudka dhinacyada abaalgudka khamaarka ee dadkan (Loba et al., 2001). Si kastaba ha noqotee, hannaanka Pavlovian wuxuu ku qaabeeyey tijaabooyinka hadda jira (CS + abaalmarin aan la hubin) waxay u muuqataa inay lama huraan tahay haddii aysan ahayn mid ku filan khibradda khamaarka.
Iyada oo ay weheliso la'aanta baahi qalab cad ah, tiro ka mid ah qaababka kale ee naqshada ayaa laga yaabaa inay gacan ka geysteen heerka isku-dheelitirka iyo isbeddelka saamaynta tijaabooyinka. Kooxuhu way ku kaladuwanaadeen muujinta guud ee guusha iyo sidoo kale kala duwanaanshaha u dhexeeya CS iyo abaalmarinta guuleysiga. In kasta oo tan laga yaabo inay gacan ka geysato kala-qaybsanaanta kooxda, haddana si dhakhso ah uma sharxi karto sababta xayawaannada leh muujinta ugu weyn ee soo-gaadhista (kooxda 100) ay u soo bandhigaan feejignaan ka yar kooxda 50. Intaa waxaa sii dheer, kooxda 0 ma helin wax dhiirrigelin ah ka hor inta aan lagu guuleysan soo-gaadhista maxkamad kasta. In kasta oo ay tani ka horjoogsatay filasho la yaab leh oo abaalmarin ah, haddana ma aysan xakameyn jiritaanka dhiirrigelinta ka hor bixinta abaalmarinta, taas oo ka jirtay dhammaan kooxaha kale. Si wax looga qabto arrintan, cilmi baarista mustaqbalka waa inay kujirtaa xaalad ay xayawaanku ku helaan abaalmarin maxkamad kasta ka dib soo-gaadhista si lama huraan u ah dhiirrigelin dhexdhexaad ah (tusaale ahaan, joogitaankiisu ma muujinayo awoodda abaalmarinta).
Xaddididda qaabeynta kale waa soo bixitaanka dabeecad isku xirnaan oo saameyn ku yeelan kara saameynta jadwalka tababarka. Marka laga soo tago shaki la'aani, xayawaanku waxay yeelan karaan dabeecado dhaqan xumo ah oo loo habeeyay inay kor uqaado xakameynta loo arko ayna yareyso dhaqdhaqaaqa DA ee aan shaki ku jirin (cali Harris et al., 2013). Sidaa darteed waa suuragal in dhinacyo aan la xakameynin ee naqshadeynta tijaabada ah ay u sahashaay xayawaanku inay ka dhabeeyaan saameynta jadwalka qaboojinta. Saamaynta noocan oo kale ah waxay gacan ka geysan kartaa jawaab celinta dhexdhexaadka ah iyo tan isbeddelka ah ee loo yaqaan 'amphetamine' ee kooxda 50 ka dib tababarka CS + sucrose. Cilmibaarista mustaqbalku waa inay duubtaa dabeecado iskeed u dhacda, marka laga reebo waxyaabaha sanka laga qaato, inta lagu gudajiro fadhiyada tababarka si loo tijaabiyo suurtagalnimada, loona xakameeyo tirakoob ahaan haddii ay soo baxdo. Sababta oo ah dabeecaddan oo kale waxaa laga fili lahaa inay ka hor tagto ama yareyso saameynta jiritaanka jiritaanka shaki la’aanta, jawaabta hoose ee jawaabta amphetamine ee kooxda 50 waa in la xoojiyaa marka la xakameynayo (qaab ahaan ama qaab ahaan). Sidaa daraadeed, naqshadeynta hadda (aan la xakameyn) waxay bixisaa tijaabo muxaafid ah oo ku saabsan saamaynta 50% CS + abaalmarinta ku saabsan dareenka amphetamine.
Marka laga hadlayo ansaxnimada dibadda, adeegsiga jiirka labka ayaa sidoo kale xaddidaya guud ahaan natiijooyinka. La'aanta xaalad cad "ciqaab" ayaa sidoo kale ka duwan khamaar, halkaas oo khasaarooyin lacageed ay caan ku yihiin oo ay ku kacaan saameynno dhiirrigelin leh (Nieuwenhuis et al., 2005; Singh iyo Khan, 2012). Awoodda aruurinta abaalmarinta ayaa sidoo kale ka maqnaata jiritaanka xaadirka ah iyo guulaha isugeynta ah ee ciyaarta mashiinka ciyaarta ayaa laga helay inay la falgalaan khalkhalgelinta DA ee dadka (Tremblay et al., 2011; Smart et al., 2013). Sidoo kale, fursadda jaakaduhu waa farqi muhiim ah oo u dhexeeya nooca hadda jira iyo khamaarka dhabta ah.
In kasta oo ay xadidan yihiin, natiijooyinka hadda jira waxay muujinayaan in abaalmarinta '50% variable CS + abaalmarinta ay ku lug yeelan karto dariiqooyinka DA ee lagu soo rogay saameynta xoojinta khamaarka (Fiorillo et al., 2003; Anselme, 2013). Dareenka is-dhaafsiga ee jawaabta AMPH kadib jadwalkan u eg-qamaarka wuxuu la mid yahay doorka doorka weyn ee DA ee khamaarka iyo saameynta daroogada maskaxda (Zack iyo Poulos, 2009), iyo wuxuu fidiyaa daraasado hore oo ku saabsan iskudarka-ka-hortagga ee dhiirigelinta khamaarka AMPH ee qamaarayayaasha cudurrada ku dhaca (Zack iyo Poulos, 2004). Natiijooyinka hadda jira waxay sidoo kale si aan toos ahayn u soo jeedinayaan in qiyaasta dhexdhexaad ah ee AMPH, oo aan keenin sii-deynta jirdhiska DA, ay u fiicnaan karto waxqabadka maskaxda ee ka jawaab celinta astaamaha abaalmarinta aan caadiga ahayn (ie, inta lagu jiro khamaarka) marka loo eego soo-gaadhista sare (ie, binge-like) qiyaaso dawooyin kiciya (cf. Vanderschuren iyo Pierce, 2010). Caawinta tooska ah ee warqadan waxaa lagu soo saari karaa iyadoo la qiimeynayo DA siideynta iyadoo laga jawaabayo 50% jadwalka CS-US ee isbadalka ah iyo qiyaasta kala duwan ee AMPH iyadoo la adeegsanayo microdialysis.
Marka laga eego dhinaca tijaabada ah, qaabka Pavlovian ee hadda jira iyo qaabkii hore ee hawl wadeenka ah ee xoojinta doorsoomayaasha labaduba waxay u muuqdaan inay abuuraan ifafaale u eg khamaarlaha cudurada aadanaha. Sidaas oo kale, waxay bixiyaan qiimo dheeri ah oo loogu talagalay howlaha khamaarka ee aadka u daran kuwaas oo tusaale u ah dhaqanka khamaarka (oo ah cabir ku-tiirsaneed) laakiin waxay leeyihiin, ilaa hadda, kaliya waxay shaqaaleysiinayaan xayawaanno caafimaad qaba, oo u dhigma kuwa khamaarka bulshada u leh. Iyada oo ku saleysan suugaanta, xayawaanka sida joogtada ah ugu dhaca abaalmarinta doorsoomayaasha ah wey ku kala duwanaan kartaa howlahan, gaar ahaan marka laga jawaabayo daroogada DA-ergic. Isku darista khamaarka jiimka ah ee howlaha khamaarka waxay u oggolaaneysaa in si nidaamsan loo horumariyo daawooyinka loogu talagalay daaweynta PG, oo laga yaabo in aan si buuxda loogu dhammayn xayawaannada caafimaadka qaba. Dib-u-habeyn dheeri ah oo ku saabsan naqshadeynta tijaabada iyo tababarka tababarka, sida kor lagu soo sharraxay, waa inay hagaajiso xiriirka ka dhexeeya xayawaanka lagu tababaray qaabkan iyo khamaarka dhabta ah ee cudurka.
Marka la eego aragtida kiliinikada-cilmiga bulshada, helitaanka in soo-gaadhista abaalmarinta 50% isbeddelka CS +, oo si dhaw ugu habboon jadwalka abaalmarinta ee mashiinka booska ganacsiga (Tremblay et al., 2011), wuxuu u beddelaa nidaamka maskaxda DA qaabab la isku halleyn karo oo waara oo soo jeedinaya in, xaaladaha qaarkood, waxqabadka khamaarka, sida daroogada xadgudubka, uu noqon karo “cudud” awood u leh inuu keeno balwadda. Si kastaba ha noqotee, cabirka saamaynta dhexdhexaadka ah iyo isbeddelada sare ee jawaab celinta 50% CS + abaalmarinta waxay soo jeedinayaan, sida daroogada xadgudubka, u janjeerka jadwalka abaalmarinta khamaarka u leh dhiirrigelinta balwadda waxay si weyn ugu xirnaan doontaa astaanta khatarta hore u jirtay ee khamaarka. Si kastaba ha noqotee, si looga badbaado shakhsiyaadka halista u leh soo-gaadhista cawaaqib xumada la xiriirta dhibaatooyinka khamaarka, waxay umuuqataa caqli gal in siyaasadaha lagu dabaqay isticmaalka iyo yareynta waxyeelada ka imaanaysa daroogada waxyeelada sidoo kale loo kordhin karo khamaarka sidoo kale.
Khilaafka dulmiga xiisaha
Qorayaashu waxay caddeeyeen in cilmi-baaristaan lagu sameeyey maqnaansho xiriir ganacsi ama dhaqaale oo laga yaabo inay noqon karto khilaafka xiisaha leh.
Mahadnaq
Baadhitaankan waxaa lagu maalgeliyey deeq ka timid The Science of Natural Science iyo Engineering Research Council ee Kanada oo uu u fidiyay Paul J. Fletcher. Waxaan si daacad ah ugu mahadnaqaynaa Marwo Djurdja Djordjevic diyaarinta tirooyinka.
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