1. ¹Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA
2. ²Neuroscience Research, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland

Correspondence: Dr A Markou, Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA. Tel: +1 858 784 7244; Fax: +1 858 784 7405; E-mail: amarkou@scripps.edu

Received 5 February 2004; Revised 8 June 2004; Accepted 9 June 2004; Published online 21 July 2004.

Abstract

Acute administration of -aminobutyric acid B (GABA_B) receptor agonists decreased nicotine, cocaine, ethanol, and heroin self-administration. GABA_B 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 GABA_B 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.