Psychophiracolon: (199-) 107. 285-249 Psychopharmacology Uokg l492 Springst- The mesolimbic dopaminergic system is implicated reinforcing cffects of nicotine in the Franklin' , Katblern M. Cocn' Paul BS Clarkc' William Conigall" Keith BJJ Fouidalion, Toronto. Onlano- Ncurobiology Cinada MSS >S1 Srlon Addicteon acatcn HJA Poyckology. MGill Univcrsity. Mortreal Olkhe Canatn LEPAntMcr HJG IY6 Phamacology and Therapulics. McGil Univecsity. Honiral Qubcc Cinio; DpinM0 Rcccited Apnl 199| Final Icrsion AmcusI qucstionabla whether hexamc Abstract. Rats #cre trained self-adminisicr nicolinc on ol nicolin brraus fixed-ratio scheduke of rcinforccment: Iofusion of tha thonium; Ihe doscs Icstcd, #ould cuert  sullicient pripberal blockadc this spceics (Romano 1981}. anlagonist chlorisondamine mculinx ccrCOrBI dnugs (most notably vcntricles Cenain dpcndcnce-prodecing Droduced susainCO fcduclion nicolne comparcd [0 Kchicle-Ireated controls. cocalne a00 4--mphelaiin: whcn adminislercd system" scitauministtanon thcir rcinforcing cfecls throughan appcar sy stcm Lan nctolibic dopamine Hcie icallt erett 6-hydroxydopaminc into of tha brain $ mcsolitbic dopaninc produccd by microinfusion acntatton syslcm Following produclion al. 1980; Pcttit et al. 1984: Manin-Iverson (Robers _ rucifus ac-umDens al, 1936; Wisc and Rompre 1969). and thc mcsolimbic Igions nrroting scl-dminitration markcdly dopaminc systcm docs #Ppcar duced for the J-ucck penod; motor impairmcnt did terzcl Jor nicotin:. lechniques indicate that br responsibl . Post morlem analysis of Newtoanaromic not appcar mnapping the Icsion produccd shoxed mcsolimbic donamincrec T6bnin brain lisuc ncuton DOSSCs nIc - of thc nucleus otinic receplors the Ievel of &ll bodics and;or den nouncco decrras in dopaminc conteni within tbe venlral tcgmcntal arca (WTA} and also and thc   ollactory  (ubcrcie. accumocns drile sTnali mOolimbic Icrminal fields (nuckcus acumbens deplalion tha snat urn Thcsc data ollic- demonstrte (hal the rcinforcing clccis of nicotine occur within the central lory [ubercle) (Clarke and Pert |935: Deulsch ctal 1987 a7,,1987: Wada 4al. 1989). Nicotinc dircctly thc   mcsolimbic   dopaminc uansor systcm; nerous projcclion plays a2 importani role cxcilcs dopamincrgic cclls of thc These Enecl Anin cgTncnIz Calabresi t 1939) . und syslemic administra - Ltro Key Nicoline Mcsolimbic dopamint Rcin- lion ol nicolinc vivc inCrcases [Ilraccllular concentra Ruros Dopaminc Nucleus accumbcns 6-Hy: of dopaminc in th: nuclcus lorccmcnl accunibrns Icminal uons droxydopaminc field in rats ([mpcralo 1986). As with psychomotor slimulanl drugs such coclinc an 4-ampoelamine of mcsolimbic Jopamine acitnior Mnderl Ipucan Ihc locomotor cil: ol systcmically-adminis- Hmtaant Thc phanacology nkolinc has much studicd, nicoline, abolished alicr ncuroloxic Ieto koown Sia Lbu Vittle bouithe neurobiological mcchanisms dopaminergic syslcm (Clarke thc mcsolimbic sons responsiblc for thc rcinforcing propertics ol this 1988a};   locomotor simulation alkaloid (Corrigall [99l2). Indccd although thcrc has produccd by focal administration nicolinc inlo Lhc cvidcnce suEgcsting that the rein- occn con erecnc 0i VTA rcgion (Reavil] and Stolcman 19904 forcingeffects of nicotine , from its action within the eauk Dala such thc   possibilily Ihese [JiSE convinaing singl: demonsira centra ncrous mesolimhic dopamina Syslcm may contribute also scIl-administra- tion of ihis faci lacking; Inlravenous rcinforcing   properlics nicolinc . This possibility by Prc-[rcaiment tian olnicolunc 4numnals k< aticnualco by tht reccnl demonsIration givcn credenc antagonist that Cc ndm with mecamylaminc , niculinic boli anlagonists rcducr nicolinc xlf: that xlective dopaniing 1981 : pcriphcrally active (Goldberg Ccntally ano edminislralion (Cotrigall 1991c; Corrigall and Corrigail and Cocn 1939). by hcxamcthonium; soupht Coen The Deeseni puuu evamimc /4o nicolinic anlagonisi which passcs the blood-brain bJr- (i) ar ailercts of nico ricr Iess rcadily (Corriga qucson_ namc/ Ic; ecumanginz Cocn 1989). Howevcr, this lne mcdiated vja constitutes #cak cvidcncc for diceci (euiru jclion . Jnd ()Is Ihe reinforcing eflect cntfa mcsolimbic dopamincsgic IclecliaI Imenrani Oferint tine reinforcemcnt? Comrall WraltII 40021420
Psychophiracolon: (199-) 107. 285-249 Psychopharmacology Springst- Uokg l492 The mesolimbic dopaminergic system is implicated in the reinforcing cffects of nicotine William Conigall" Keith BJJ Franklin' , Katblern M. Cocn' Paul BS Clarkc' Ncurobiology Srlon Addicteon acatcn Fouidalion, Toronto. Onlano- Cinada MSS >S1 LEPAntMcr Poyckology. MGill Univcrsity. Mortreal Olkhe Canatn HJA DpinM0 Phamacology and Therapulics. McGil Univecsity. Honiral Qubcc Cinio; HJG IY6 Rcccited Apnl 199| Final Icrsion AmcusI Abstract. Rats #cre trained self-adminisicr nicolinc on ol nicolin brraus qucstionabla whether hexamc fixed-ratio scheduke of rcinforccment: Iofusion of tha thonium; Ihe doscs Icstcd, #ould cuert  sullicient mculinx anlagonist chlorisondamine ccrCOrBI pripberal blockadc this spceics (Romano 1981}. vcntricles Droduced susainCO fcduclion nicolne Cenain dpcndcnce-prodecing dnugs (most notably scitauministtanon comparcd [0 Kchicle-Ireated controls. cocalne a00 4--mphelaiin: whcn adminislercd system" Lan nctolibic dopamine sy stcm Hcie icallt appcar erett thcir rcinforcing cfecls throughan produccd by microinfusion 6-hydroxydopaminc into acntatton of tha brain $ mcsolitbic dopaninc syslcm rucifus ac-umDens Following produclion (Robers _ al. 1980; Pcttit et al. 1984: Manin-Iverson Igions nrroting scl-dminitration markcdly al, 1936; Wisc and Rompre 1969). and thc mcsolimbic duced for the J-ucck penod; motor impairmcnt did dopaminc systcm docs #Ppcar terzcl Jor nicotin:. not appcar br responsibl . Post morlem analysis of Newtoanaromic mnapping lechniques indicate that brain lisuc shoxed the Icsion produccd T6bnin mcsolimbic donamincrec ncuton DOSSCs nIc - nouncco decrras in dopaminc conteni of thc nucleus otinic receplors the Ievel of &ll bodics and;or den accumocns and thc   ollactory  (ubcrcie. sTnali drile within tbe venlral tcgmcntal arca (WTA} and also deplalion tha snat urn Thcsc data demonstrte (hal mOolimbic Icrminal fields (nuckcus acumbens ollic- the rcinforcing clccis of nicotine occur within the central lory [ubercle) (Clarke and Pert |935: Deulsch ctal 1987 nerous systcm; thc   mcsolimbic   dopaminc uansor a7,,1987: Wada 4al. 1989). Nicotinc dircctly projcclion plays a2 importani role These Enecl cxcilcs dopamincrgic cclls of thc Anin cgTncnIz Ltro Calabresi t 1939) . und syslemic administra - Key Ruros Nicoline Mcsolimbic dopamint Rcin- lion ol nicolinc vivc inCrcases [Ilraccllular concentra lorccmcnl Nucleus accumbcns Dopaminc 6-Hy: uons of dopaminc in th: nuclcus accunibrns Icminal droxydopaminc field in rats ([mpcralo 1986). As with psychomotor slimulanl drugs such coclinc an 4-ampoelamine acitnior of mcsolimbic Jopamine Ipucan Mnderl Ihc locomotor Hmtaant Thc phanacology nkolinc has much studicd, cil: ol systcmically-adminis- Lbu Ieto nicoline, Vittle koown bouithe neurobiological mcchanisms Sia abolished alicr ncuroloxic sons responsiblc for thc rcinforcing propertics ol this thc mcsolimbic dopaminergic syslcm (Clarke alkaloid (Corrigall [99l2). Indccd although thcrc has 1988a};   locomotor simulation produccd by focal administration occn con erecnc 0i cvidcnce suEgcsting that the rein- nicolinc inlo Lhc eauk from its action within the VTA rcgion (Reavil] and Stolcman 19904 forcingeffects of nicotine , centra ncrous Dala such Ihese [JiSE thc   possibilily convinaing singl: demonsira tion of ihis faci Inlravenous scIl-administra- mesolimhic dopamina Syslcm may contribute also lacking; tian olnicolunc 4numnals k< aticnualco rcinforcing   properlics nicolinc . by Prc-[rcaiment This possibility niculinic boli givcn Cc ndm credenc with mecamylaminc , antagonist that by tht reccnl demonsIration Ccntally ano 1981 : that xlective dopaniing anlagonists rcducr nicolinc xlf: pcriphcrally active (Goldberg edminislralion (Cotrigall Corrigail and Cocn 1939). by hcxamcthonium; 1991c; Corrigall and nicolinic anlagonisi which passcs the blood-brain bJr- Coen The Deeseni puuu soupht evamimc /4o ricr Iess rcadily (Corriga Cocn 1989). Howevcr, this qucson_ namc/ (i) ar Ic; ecumanginz ailercts of nico constitutes #cak cvidcncc for cntfa reinforcing eflect lne mcdiated vja diceci (euiru jclion . Jnd ()Is Ihe mcsolimbic dopamincsgic IclecliaI Imenrani Oferint WraltII Comrall tine reinforcemcnt? 40021420