Curr Neuropharmacol. 2011 Mar; 9(1): 63–67.
ikhonkco: 10.2174/157015911795017218
Hisatsugu Miyata,a,* Michio Itasaka,b uNaofumi Kimura,c kwaye Kazuhiko Nakayamaa
Eli nqaku liye khankanywe ngu amanye amanqaku kwi-PMC.
Abstract
Injongo yolu phononongo yangoku yayikukuphanda ukuba umsebenzi womvuzo wobuchopho uyehla ngexesha lokurhoxa kwi-nicotine kunye ne-methamphetamine, kwaye ingaba umsebenzi owehlileyo womvuzo unxulumene nokuchaswa ngexesha lokurhoxa kula machiza. Ngenxa yaloo njongo, iimpuku ze-Sprague-Dawley zamadoda zazifakwe ngokungapheliyo kunye ne-9 mg / kg ngosuku lwe-nicotine, okanye nge-6 mg / kg ngosuku lwe-methamphetamine usebenzisa i-osmotic minipumps. Kwi-intracranial self-stimulation (ICSS) paradigm, ukufakwa okungapheliyo kwenikotine kunye ne-methamphetamine kunciphisa imida ye-hypothalamic ICSS, ngelixa abachasi babo, i-mecamylamine kunye ne-haloperidol benyuse i-ICSS kwiimpuku eziphathwa nge-nicotine kunye ne-methalymphetamine. Kwi-conditioned place aversion paradigm, i-mecamylamine kunye ne-haloperidol zivelise indawo yokuzonda kwi-nicotine- kunye neempuku ezifakwe kwi-methamphetamine, ngokulandelelanayo. Okubangela umdla kukuba, ukunyuka kwemivuzo ye-ICSS kunye nokucaphuka kwendawo ngexesha lokurhoxiswa kwe-nicotine ye-mecamylamine kuphantse kwafana kubukhulu njengoko kubonwe ngexesha lokurhoxiswa kwe-haloperidol-precipitated methamphetamine. Uphononongo lwangoku lubonisa ukuba i-1) umsebenzi womvuzo wengqondo wehlile ngexesha lokurhoxiswa kwe-nicotine kunye ne-methamphetamine, kunye ne-2) ukuncipha komsebenzi womvuzo kunokubonisa imeko engathandekiyo (ukuthiya) ngexesha lokurhoxa kwi-nicotine kunye ne-methamphetamine.
1. INTSHAYELELO
Ubungqina beklinikhi bubonisa ukuba iimpawu ezichaphazelayo ze-abstinence syndrome zinokubaluleka ngakumbi kwiminqweno yeziyobisi kunye nokubuyela ekusetyenzisweni kweziyobisi okunyanzelekileyo kuneempawu zokurhoxa [1-3]. Ngeso sizathu, imiba echaphazelekayo yokuxhomekeka kumachiza iphandwe ngokubanzi kusetyenziswa iintlobo ezahlukeneyo zeeparadigms zovavanyo. Phakathi kwazo, ubuchule bokuzenzela i-intracranial self-stimulation (ICSS) busetyenziswa ngokubanzi ukulinganisa umsebenzi womvuzo wobuchopho. Kwizifundo zezilwanyana, ulawulo oluqatha lwechiza lokusetyenziswa kakubi kunciphisa imivuzo ye-ICSS [4, 5] kwaye oku kwanda kobuntununtunu ekuvuseleleni kuthathwa njengomlinganiselo we-euphoria eyenziwe ngamachiza [6]. Ngaphaya koko, kucingelwa ukuba umvuzo we-ICSS unokuthotywa emva kokulawulwa okuphindaphindiweyo kwechiza lokusetyenziswa kakubi, okubangelwa utshintsho lwe-neuroadapted yeenkqubo zomvuzo wobuchopho, kunye nokubonakalisa i-dysphoria ngexesha lokurhoxiswa kwechiza [7, 8]. Izifundo ezininzi zibonise ukuphakama kwi-ICSS imivuzo yomvuzo ngexesha lokurhoxa kwiintlobo ezahlukeneyo zeziyobisi zokuxhatshazwa kubandakanya i-amphetamine [9], icocaine [6], amayeza [10], i-ethanol [11], kunye nicotine [12], zonke ezixhasa le ngcamango ikhankanywe ngasentla. Ke ngoko, uphononongo lwangoku lwenzelwe ukucacisa ukuba ngaba ukuphakama kumvuzo we-ICSS kunxulumene nemeko engathandekiyo yokurhoxa, ngakumbi kugxilwe kwiintlobo ezimbini ezahlukeneyo ze-psychostimulants, inikotini kunye ne-methamphetamine.
2. IMPAHLA NENKQUBO
2.1. Izilwanyana
Iigundane ezingamashumi asixhenxe anesibini ze-Sprague-Dawley (332-396 g) ezifunyenwe kwi-Clea Japan Inc. (Tokyo) zahlaliswa ngabanye kwigumbi lezilwanyana kwiqondo lokushisa elilawulwayo (22 ± 2 ºC) kunye nomjikelezo wokukhanya / omnyama we-12/12 iiyure (kukhanya ngo-8:00 AM). Impuku nganye yondliwa i-15 g yokutya ngosuku (amanzi afumaneka simahla) ngalo lonke ixesha lovavanyo, ngaphandle kwesithuba seentsuku ezi-3 phambi kunye neentsuku ezisi-7 emva kotyando. Olu vavanyo lwenziwe ngokuhambelana neMigaqo yeLabhoratri yoLondolozo lweZilwanyana kwiYunivesithi yaseJikei yeSikolo sezoNyango.
2.2. Zi yobisi
(-)-nicotine hydrogen tartrate (Sigma, St. Louis, MO, USA), mecamylamine hydrochloride (Sigma), (-) methamphetamine hydrochloride (Dainipponn Seiyaku, Japan), kunye ne-haloperidol hydrochloride (Sigma) zaye zachithwa kwi-saline kwaye zafakwa umthamo we-1.0 ml / kg.
2.3. Intracranial Self-Stimulation
2.3.1. Izixhobo
Igumbi elisebenzayo eliqhelekileyo le-29.5 (W) x 23.5 (L) x 28.7 (H) cm (ENV-008; i-Med Associates, Inc., i-St. Albans, i-VT, i-USA) ixhotyiswe nge-lever enye kunye ne-cue light ngaphezu kwe-lever. kudonga olungaphambili kwaza kwasetyenziswa isibane sendlu kudonga olungasemva. Iindonga zecala zenziwe ngePlexiglas ecacileyo.
2.3.2. Ukuhlinzwa
Amagundane ayenziwe i-anesthetized nge-sodium pentobarbital (50mg / kg, ip) kwaye yalungiswa nge-electrode ye-bipolar yensimbi engenasici (i-Neuroscience, eJapan) kwi-hypothalamus esecaleni (ilungelelanisa i-3.8mm ngasemva kwe-bregma; i-1.4mm ecaleni ukuya kumgca ophakathi; i-8.4mm ye-ventral ukuya kwi-ventral ukuya kwi-XNUMX. dura) ngokweatlasi yePaxinos kunye neWatson [13]. Ukuchasana nayo nayiphi na i-asymmetries yobuchopho enokwenzeka, isiqingatha seempuku safumana ukufakelwa kwicala lasekunene lobuchopho, kunye nelinye kwicala lasekhohlo.
2.3.3. Inkqubo
Kwiiseshoni zoqeqesho ze-ICSS, isibane sendlu kunye nesibane se-cue sivuliwe kwaye i-stimuli yombane inikwe ixesha ngalinye ngokukhawuleza emva kokuba i-rat icinezele i-lever. I-stimuli yayiquka i-1.5 msec i-cathodal pulses ye-cathodal pulses, ihanjiswe nge-100 Hz ye-150 msec kunye ne-fixed current ye-120 μA. Iseshoni yoqeqesho nganye ithathe i-15 min. Uqeqesho lwe-ICSS lwanikezelwa ubuncinane kwiintsuku ze-6 kwaye lwaqhubeka de inani le-lever press libe ngaphezu kwe-30 ngomzuzu ngeentsuku ezi-3 ezilandelelanayo.
Ukulinganisa isiseko sokuphendula kwe-ICSS, uvavanyo olusisiseko lwenziwa kwimizuzu eli-15 phambi kovavanyo lomqobo lwe-ICSS. Inkqubo yovavanyo olusisiseko yayifana naleyo yoqeqesho lwe-ICSS. Uvavanyo lwe-ICSS threshold test lwenziwe ngemigqomo ye-11 yemizuzu emi-3 yahlulwe ngumzuzu o-1 wokuphuma. Ngexesha lokuphuma, isibane sendlu kunye nesibane se-cue sacinywa. Kumgqomo ngamnye wovavanyo, ezi zibane zavulwa kwaye iimpuku zafumana uvuselelo lombane emva koshicilelo lwe-lever nganye. Kuyo yonke imigqomo, umbane wokuvuselela umbane wehla nge-10 μA ukusuka kwi-120 μA ukuya kwi-20 μA ngokuhla.
Isiseko esizinzileyo sokuphendula kwe-ICSS sasekwa kuzo zonke iimpuku phambi kokufakelwa kweeminipumps. Ngomhla woku-1, impompo encinci ye-osmotic (Alzet 2001, Alza Corporation, CA, USA) enesantya sokuhamba kwe-1.03 μl/h ezaliswe inikotine okanye i-methamphetamine kwi-saline yafakwa ngaphantsi kwesikhumba kwiimpuku eziye zafakwa isitofu nge-diethylether. I-concentration ye-nicotine kunye ne-methamphetamine yalungiselelwa ukungafani kobunzima bomzimba, kodwa yayimalunga ne-116 kunye ne-77.3 mg / ml, okubangelwa ukunyanzeliswa kwe-subcutaneous ngokuqhubekayo kwinqanaba le-9 mg / kg ngosuku lwe-nicotine kunye nomlinganiselo we-6 mg / kg. ngosuku lwemethamphetamine ngokwendlela yesifundo sangaphambili [14]. Uvavanyo lomda we-ICSS lwenziwa ngomhla we-2, 4, kunye no-6 emva kokufakelwa kwee-minipumps.
Ngomhla we-7 emva kokufakelwa kwe-minipump, iigundane zifumana i-mecamylamine (0.0, 0.1, 0.5, 1.0 mg / kg, sc) kumaqela e-nicotine- kunye ne-saline-infused, okanye i-haloperidol (0.0, 0.1, 0.25, 0.5 mg / kg, sc) kumaqela e-methamphetamine- kunye ne-saline-efakwe kwi-saline, i-15 min ngaphambi kokuqala kweseshoni yokuvavanya i-ICSS, usebenzisa i-design yangaphakathi ye-Latin-square. Izilwanyana bekufuneka zibuyele kwisiseko somda we-ICSS ubuncinci kwiseshoni enye ye-ICSS phambi komchasi olandelayo okanye iinaliti zesithuthi.
2.3.4. Imbali
Iimpuku zanikelwa nge-anesthesia enzulu nge-sodium pentobarbital. Ingqondo yasuswa kwaye yagcinwa kwi-10% yesisombululo se-formaldehyde. Ubuchopho bunqunyulwe kubukhulu be-100 μm kwaye incam ye-electrode yahlolwa nge-microscopically.
2.4. Umqathango Indawo Aversion
2.4.1. Isixhobo
Ukulungiswa kwendawo kwenziwa ngokwendlela yeSuzuki okqhubekayo. [15, 16]. I-apparatus yayine-shuttlebox (30 × 60 × 30 cm: w × l × h) eyahlulahlulwe ibe ngamacandelo amabini alinganayo. Elinye icandelo lalimhlophe linomgangatho owenziweyo lize elinye libe mnyama nomgangatho ogudileyo.
2.4.2. Inkqubo
Ngomhla woku-1, iigundane zalungiswa nge-nicotine-, i-methamphetamine-, okanye i-saline-containing osmotic minipumps phantsi kweemeko ezifanayo nezo zichazwe kuphononongo lwe-ICSS.
Ekuseni (9:00) ngosuku lwe-7 ye-nicotine okanye i-methamphetamine infusion, iigundane zafakwa phantsi kwesikhumba kunye nomchasi weyeza lokuvavanya (i-mecamylamine okanye i-haloperidol), okanye i-saline (1.0 ml / kg), kwaye ngokukhawuleza ivalelwa kwi-compartment enye. izixhobo zokuvavanya i-60 min. Ngokuhlwa (21:00) ngosuku olufanayo, iigundane zaye zaphathwa nge-saline okanye umchasi (i-mecamylamine okanye i-haloperidol), ngokulandelanayo, kwaye zivalelwe kwelinye igumbi le-60 min. I-pairings yenaliti (umchasi okanye i-saline) kunye ne-compartment (emhlophe okanye emnyama) yayichasene kuzo zonke izifundo. Iigundane zokulawula kwi-nicotine-, i-methamphetamine-, kunye namaqela afakwe i-saline afakwe nge-saline endaweni ye-mecamylamine okanye i-haloperidol kwiseshoni yokulungelelanisa. Emva kweenaliti ze-saline, iigundane zazivalelwe kwelinye igumbi ekuseni kwaye kwelinye igumbi ngokuhlwa.
Ngentsasa yosuku lwe-8, iimvavanyo ze-conditioning zenziwa ngolu hlobo lulandelayo: ulwahlulo olwahlula amacandelo amabini luphakanyiswe ukuya kwi-12 cm ngaphezu komgangatho, kwaye iqonga elingathathi hlangothi lifakwe ecaleni kwe-seam eyahlula amacandelo. Ixesha elichithwe kwicandelo ngalinye ngexesha leseshoni ye-900 lilinganiswa ngokuzenzekelayo nge-sensor ye-infrared beam (kn-80, Natsyme Seisakusho, Tokyo, Japan).
2.5. Uvavanyo lweempawu zokurhoxiswa kweSomatic
Kuvavanyo lwe-ICSS, impuku nganye yafakwa kwigumbi lokujonga iplastiki ecylindrical ngoko nangoko emva kokupheliswa kweseshoni yomvuzo we-ICSS emva kokulawulwa kwe-mecamylamine okanye i-haloperidol, kunye neempawu zokurhoxiswa kwe-somatic zabonwa i-10 min. Ngexesha lovavanyo lweempawu zokurhoxa, ukuphindaphinda kweempawu zokuziyeka zarekhodwa kusetyenziswa isikali se-opiate-abstinence esiguqulelwe ukuphawula i-nicotine okanye i-methamphetamine yokuziyeka [1]. Abavavanyi baye bangaboni ukunyangwa kwempuku nganye. Kuvavanyo lwe-CPP, imiqondiso yokurhoxa kwe-somatic yajongwa ngendlela efanayo naleyo kuvavanyo lwe-ICSS ngaphandle kwento yokuba ukuqwalaselwa kweempawu zokuziyeka ze-somatic kwenziwa kwisixhobo se-CPP.
2.6. Uhlalutyo lwedatha
Kumlinganiselo wokuphendula kwe-ICSS, inani lokomeleza ngomzuzu ngamnye kumgqomo ngamnye lisetyenziswe njengomlinganiselo. Ngeentsuku zovavanyo, inani lokuqiniswa kumbane ngamnye latshintshwa libe yipesenti yesiseko esifunyenwe ngolo suku. Ukumisela umda we-ICSS, i-S-shape curve yafakelwa ngabanye ngokwemodeli ye-sigmoid-Gompertz. Ukusebenzisa le modeli, umsinga wombane ophembelela i-50% yempendulo esisiseko yamiselwa njengomqobo we-ICSS. Zonke iinkcukacha zahlaziywa kusetyenziswa iindlela ezimbini ngaphakathi-izifundo eziphindaphindiweyo-ukulinganisa uhlalutyo lwe-variance (ANOVA) elandelwa yi-Tukey ye-Studentized Range Method emva kokuqwalaselwa kwesiphumo esibalulekileyo sonyango lweemeko zonyango kwi-ANOVA.
Amanqaku okumisela amele ixesha elichithwe kwindawo edityaniswe neziyobisi kuthatyathwe ixesha elichithwe kwindawo edityaniswe nesithuthi kwaye ichazwa njengentsingiselo ± SEM Idatha yokuziphatha yavavanywa ngokwezibalo ngeendlela ezimbini zokuphinda-phinda imilinganiselo ye-ANOVA, eyayisetyenziselwa ukumisela. iimpembelelo zonyango kwi-antagonist-induced place conditioning. Xa i-ANOVA ibonise ubukho bempembelelo ebalulekileyo, uhlalutyo olongezelelweyo lwenziwa kunye ne-Tukey's Studentized Range Method.
3. IZIPHUMO
3.1. ICSS Thresholds
Ngexesha lolawulo olungapheliyo, i-nicotine (F (2, 35) = 5.28, P<0.01) kunye ne-methamphetamine (F (2, 35) = 7.62, P<0.01) yehle kakhulu imida yokuvuza ye-ICSS. Ukuthelekiswa kweendlela zomntu ngamnye kubonise iziphumo ezibalulekileyo ngosuku lwe-4 kunye nosuku lwe-5 lwe-nicotine infusion (P<0.05), kunye nosuku lwe-2, usuku lwesi-4, kunye nosuku lwe-5 lwe-methamphetamine infusion (P<0.05).
Njengoko kubonisiwe kuMfanekiso.11), kwiimpuku ezifakwe kwi-nicotine engapheliyo kunye ne-methamphetamine, i-mecamylamine (F (1, 47) = 9.59, P<0.01) kunye ne-haloperidol (F (1, 47) = 10.64, P<0.01) ivelise ukuphakama okubalulekileyo kwi-ICSS imida yokuvuza, ngokulandelelanayo. Ukuthelekiswa kweendlela zomntu ngamnye kubonakalise iziphumo ezibalulekileyo kwi-1.0 mg / kg mecamylamine (P<0.05) kunye ne-0.25 kunye ne-0.5 mg / kg haloperidol (P<0.05). Kwakungekho siphumo sibalulekileyo sedosi nokuba kwiimpuku ezifakwe nicotine (F (3, 47) = 1.87, P>0.05) okanye kwiimpuku ezifakwe kwimethamphetamine (F (3, 47) = 2.24, P> 0.05), okanye unyango × ukusebenzisana kwedosi nokuba kwiigundane ezifakwe kwi-nicotine (F (3, 47) = 1.56, P>0.05) okanye kwiimpuku ezifakwe kwimethamphetamine (F(3, 47) = 1.77, P> 0.05).
3.2. I-Conditioned Place Aversion (CPA)
Njengoko kubonisiwe kuMfanekiso.22), iimpuku zokulawula ityuwa azibonakalisi kukhetha nakweliphi na igumbi. I-Mecamylamine kunye ne-haloperidol azizange zivelise indawo ebalulekileyo okanye indawo engathandekiyo kwiigundane ezifakwe i-saline. Kwelinye icala, mecamtlamine (F (1, 47) = 8.62, P<0.01) kunye ne-haloperidol (F (1, 47) = 11.28, P<0.01) ivelise indawo engathandekiyo kwi-nicotine engapheliyo- kunye ne-methamphetamine-ifakwe iigundane, ngokulandelanayo. Ukuchaswa kwendawo ebalulekileyo kubonwe kwi-1.0 mg / kg mecamylamine (P<0.01) kunye ne-0.25 kunye ne-0.5 mg / kg haloperidol (P <0.05 kunye ne-P <0.01). Kwakungekho siphumo sibalulekileyo sedosi nokuba kwiimpuku ezifakwe nicotine (F (3, 47) = 1.98, P>0.05) okanye kwiimpuku ezifakwe kwimethamphetamine (F (3, 47) = 2.56, P> 0.05), okanye unyango × ukusebenzisana kwedosi nokuba kwiigundane ezifakwe kwi-nicotine (F (3, 47) = 1.74, P>0.05) okanye kwiimpuku ezifakwe kwimethamphetamine (F (3, 47) = 2.28, P> 0.05).
3.3. Iimpawu zeSomatic
Inani lilonke leempawu ze-somatic alahlukanga phakathi kwe-nicotine- kunye neempuku ezinetyuwa ngexesha lolawulo lwe-mecamylamine nokuba kulingo lwe-ICSS (F (1, 47) = 2.02, P>0.05) okanye kumfuniselo weCPA (F (1, 47) = 1.87, P>0.05). Ngaphaya koko, abazange bahluke phakathi kwe-methamphetamine- kunye neempuku ezinetyuwa ngexesha lolawulo lwe-haloperidol nokuba kulingo lwe-ICSS (F (1, 47) = 1.53, P>0.05) okanye kumfuniselo weCPA (F (1, 47) = 2.33, P> 0.05).
3.4. Uhlalutyo lwe-Histological
Iziphumo zohlalutyo lwe-histological lubonise ukuba iingcebiso ze-electrode zibekwe kwindawo ye-hypothalamus esecaleni, kwinqanaba elingaphambili / elingasemva ukusuka kwi--3.84 mm ukuya kwi-4.20 mm ukusuka kwi-bregma. Akuzange kubonakale kukho umahluko phakathi kweendawo ze-electrode zokulawula kunye nezilwanyana zokulinga (Fig. 33).
4. UKUQUKA
Iziphumo zophononongo lwangoku zibonisa ukuba ulawulo olungapheliyo lwenikotini kunye ne-methamphetamine yehlisa imida yokuvuza ye-ICSS, ngelixa abachasi babo, i-mecamylamine kunye ne-haloperidol benyusa imivuzo ye-ICSS kwaye baphembelele i-CPA kwiimpuku eziphathwa nge-nicotine kunye ne-methamphetamine, ngokulandelelanayo. Ngokumalunga notshintsho kumvuzo wokujikeleza kwengqondo ngexesha lokurhoxa, kuye kwaxoxwa ukuba, njengoko ukuxhomekeka kukhula, i-neuroadaptations yenzeke ngaphakathi kweesekethe zobuchopho ezifanayo ezilamla ukomeleza okanye iziphumo ezivuzayo zeziyobisi zokusetyenziswa gadalala kulandela ulawulo olubukhali, olukhokelela ekubonakalisweni kokuchaphazeleka. iimpawu zokurhoxa xa uyeka iziyobisi [7, 8]. Ngokungqinelana nolu luvo, uphononongo lwangoku lubonise ukuba inikotini kunye ne-methamphetamine zibonise ukuncipha kwemivuzo ye-ICSS ngexesha lolawulo olubukhali, kunye nokwanda ngexesha lokurhoxa komchasi. Ezinye iziyobisi zokusetyenziswa kakubi njengecocaine [6], amayeza [10], kunye ne-ethanol [11] ziye zaxelwa ukuba ziphembelele iipatheni ezifanayo zeziphumo kwimilinganiselo yomvuzo ye-ICSS. Umbuzo malunga nokuba olo tshintsho kwi-brain reward circuitry lwanele ukuhlawula imiphumo emibi echaphazelekayo yokurhoxiswa sele iphantsi kophando. I-paradigm ye-CPA isalathiso sokuziphatha esiluncedo nesinovakalelo ukubona ukurhoxa, njengoko kuchaziwe kwizifundo zangaphambili ezibandakanya inikotini [15, 16] kunye neziyobisi [17, 10]. Kuphononongo lwangoku, i-mecamylamine kunye ne-haloperidol zenze i-CPA kwiidosi ezibonisa ukuphakama kwi-ICSS imida yomvuzo, icebisa ukuba ukuphakama kumvuzo we-ICSS kunokuthintela ukuchaswa ngexesha lokurhoxa kwi-nicotine kunye ne-methamphetamine. Kwelinye icala, i-mecamylamine kunye ne-haloperidol aziphumelelanga ukwenza iimpawu zokurhoxa. Iimpawu zeSomatic zokurhoxa kwi-psychostimulants zaziwa zibuthathaka kunezo zivela kwi-opiates, barbiturates kunye notywala. Ngapha koko, kunzima kakhulu ukujonga iimpawu zokurhoxa ezibangelwa ngabachasi be-nicotine kunezo zifunwa kukurhoxa ngokuzenzekelayo [12]. Okubangela umdla kukuba, kuphononongo lwangoku, ukunyuswa kwemivuzo ye-ICSS kunye nokucaphuka kwendawo ngexesha lokurhoxiswa kwe-nicotine kuphantse kwafana nobukhulu njengoko kubonwa ngexesha lokurhoxa kwe-methamphetamine, enokuthi ibonise ukuba ukwehla komsebenzi womvuzo wengqondo, okukhokelela ekurhoxeni, akunakuhluka kakhulu. Ubunzulu phakathi kwe-nicotine kunye ne-methamphetamine, kungakhathaliseki iziphumo ezibukhali zala machiza kwinkqubo yomvuzo. Ngamanye amazwi, kucingelwa ukuba i-neuroadaptations kumvuzo wokujikeleza kwengqondo ikhula phantse ukuya kumanqanaba afanayo phakathi kwe-nicotine kunye ne-methamphetamine, nangona ivuselela inkqubo yomvuzo ukuya kwinqanaba elahlukileyo nge-acute methamphetamine yomelele kune-nicotine ebukhali. Nangona kunjalo, uphando olongezelelweyo luyafuneka ukucacisa lo mbuzo ngokusebenzisa uluhlu olubanzi lweedosi zamachiza okanye ezinye iintlobo zeeparadigms zovavanyo.
Ukuqukumbela, uphononongo lwangoku lubonisa ukuba i-1) umsebenzi womvuzo wengqondo wehla ngexesha lokurhoxiswa kwe-nicotine kunye ne-methamphetamine, kunye ne-2) ukuncipha komsebenzi womvuzo kunokubonisa imeko engathandekiyo (i-aversion) ngexesha lokurhoxa kwi-nicotine kunye ne-methamphetamine.
AMAKHODI
Olu pho nonongo luxhaswe ngokuyinxenye ngezibonelelo ezivela kwiSebe lezeMfundo, iNkcubeko, iMidlalo, iSayensi kunye neTekhnoloji yaseJapan (No. 16591166), kunye neSiseko soPhando lokutshaya.
IZALATHISO
;