title: Injection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens reduces cocaine self-administration in rats.
abstract: Cocaine- and amphetamine-regulated transcript (CART) peptides appear to modulate various effects of psychostimulant drugs. Injections of CART peptide into the nucleus accumbens (NAcc) inhibit locomotion produced by systemic injections of the psychostimulants cocaine and amphetamine. Intra-NAcc injections of CART peptide also inhibit locomotion produced by microinfusions of dopamine into the NAcc, suggesting that the effects of CART peptides may be due to an interaction with the dopaminergic system in the NAcc. We sought to determine if this inhibitory effect of CART peptide generalizes to other measures of dopaminergic function such as reward/reinforcement by testing the effect of bilateral intra-NAcc CART infusions (0, 0.25, 1.0 and 2.5 microg per side) on cocaine and food self-administration. One group of rats self-administered cocaine (0.75 mg/kg per 140 microl IV infusion) on a progressive ratio schedule. A separate group received 45 mg food pellets on the same progressive ratio schedule. Bilateral intra-NAcc injections of CART peptide dose-dependently decreased the number of cocaine infusions, the breakpoint of cocaine self-administration, and the total number of bar presses on the cocaine-associated lever. There were no effects of CART injections on the breakpoint for food reward. Thus, we conclude that injections of CART into the NAcc appear to functionally antagonize a major site of action for cocaine self-administration in rats.
authors.affiliation: Department of Behavioral Neuroscience, L470, Oregon Health & Science University, School of Medicine, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Jaworski
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Hansen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kuhar
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mark
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections / Q000379:methods; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein