title: Repeated administration of the GABAB receptor agonist CGP44532 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine-seeking in rats.
abstract: Acute administration of gamma-aminobutyric acid B (GABAB) receptor agonists decreased nicotine, cocaine, ethanol, and heroin self-administration. GABAB receptor agonists also decreased cue-induced cocaine craving or seeking in humans and animals, respectively. The present study investigated the effects of repeated subcutaneous administration of the GABAB receptor agonist CGP44532 on nicotine- and food-maintained responding under a fixed ratio 5 schedule of reinforcement. The second part of the study determined whether contingent presentation of previously nicotine-associated cues reinstated extinguished nicotine-seeking behavior, and whether acute subcutaneous CGP44532 administration affected cue-induced reinstatement of extinguished nicotine-seeking behavior. The results indicated that repeated administration of 0.25 mg/kg CGP44532 selectively decreased nicotine self-administration compared to food-maintained responding during the first 7 days of treatment. Repeated administration of 0.5 mg/kg/day CGP44532 nonselectively decreased both nicotine- and food-maintained responding. Contingent presentation of previously nicotine-associated cues reinstated extinguished nicotine-seeking behavior. Further, acute CGP44532 administration (0.125 and 0.25 mg/kg) decreased cue-induced reinstatement of nicotine-seeking behavior. In summary, the present results indicated that 0.25 mg/kg/day CGP44532 selectively decreased nicotine self-administration compared to food-maintained responding, and acute administration of CGP44532 (0.125 and 0.25 mg/kg) dose-dependently decreased cue-induced reinstatement of nicotine-seeking behavior.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Paterson
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Froestl
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant; D003463:Cues; D005502:Food; D058786:GABA-B Receptor Agonists; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D010721:Phosphinic Acids; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000523:psychology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; D058786:GABA-B Receptor Agonists; D018722:Nicotinic Agonists; D063065:Organophosphonates; D010721:Phosphinic Acids; D005680:gamma-Aminobutyric Acid; D009538:Nicotine