Neil E Paterson1, Wolfgang Froestl, Athina Markou. 1. Department of Neuropharmacology CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract
RATIONALE: Previous work has indicated a potential role for gamma-aminobutyric acid-B (GABA(B)) receptor agonists in treating drug addiction in humans. Specifically, GABA(B) receptor agonists decreased cocaine, heroin and nicotine self-administration in rats. OBJECTIVES: The purpose of the present studies was to extend previous findings by assessing the effects of additional GABA(B) receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats. METHODS: Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABA(B) receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules. RESULTS: Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function ( r=0.61). Both CGP44532 and (-)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule. CONCLUSION: The present data demonstrate that administration of GABA(B) receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABA(B) receptor agonists as therapeutics for smoking cessation.
RATIONALE: Previous work has indicated a potential role for gamma-aminobutyric acid-B (GABA(B)) receptor agonists in treating drug addiction in humans. Specifically, GABA(B) receptor agonists decreased cocaine, heroin and nicotine self-administration in rats. OBJECTIVES: The purpose of the present studies was to extend previous findings by assessing the effects of additional GABA(B) receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats. METHODS: Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABA(B) receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules. RESULTS:Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function ( r=0.61). Both CGP44532 and (-)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule. CONCLUSION: The present data demonstrate that administration of GABA(B) receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABA(B) receptor agonists as therapeutics for smoking cessation.
Authors: Kelly P Cosgrove; Irina Esterlis; Graeme F Mason; Frederic Bois; Stephanie S O'Malley; John H Krystal Journal: Neuropharmacology Date: 2011-01-27 Impact factor: 5.250
Authors: Andrew C Harris; Paul R Pentel; Danielle Burroughs; Mylissa D Staley; Mark G Lesage Journal: Psychopharmacology (Berl) Date: 2011-04-15 Impact factor: 4.530