title: The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding.
abstract: Cannabinoid CB(1) receptor antagonists can decrease methamphetamine self-administration. This study examined whether the CB(1) receptor antagonist AM251 [N-(piperidin-1-yl)-5-(4-indophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] modifies reinstatement in rats that previously self-administered methamphetamine. Rats (n=10) self-administered methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 2 schedule. Non-contingent methamphetamine (0.01-1.78 mg/kg, i.v.) yielded responding for saline (reinstatement) that was similar to responding for self-administered methamphetamine. AM251 (0.032-0.32, i.v.) did not affect methamphetamine-induced reinstatement but significantly attenuated Delta(9)-tetrahydrocannabinol (2.0 mg/kg, i.p.)-induced hypothermia. These data fail to support a role for endogenous cannabinoids or cannabinoid CB(1) receptors in reinstatement and, therefore, relapse to stimulant abuse.
authors.affiliation: Cajal Neuroscience Institute, Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
authors.forename: Sherin Y
authors.initials: SY
authors.lastname: Boctor
authors.forename: Joe L
authors.initials: JL
authors.lastname: Martinez
authors.forename: Wouter
authors.initials: W
authors.lastname: Koek
authors.forename: Charles P
authors.initials: CP
authors.lastname: France
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012055:Reinforcement Schedule; D012646:Self Administration; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D008694:Methamphetamine; D013759:Dronabinol