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Behav Pharmacol. 1998 May;9(3):195-206.

The GABAB agonist baclofen modifies cocaine self-administration in rats.

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  • 1Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA.

Abstract

The present experiments were conducted to examine further the ability of GABAergic compounds to modify the reinforcing effects of cocaine. In male Sprague-Dawley rats, behaviour was maintained under a fixed-ratio (FR)-5 with a 240 s timeout (TO) multiple schedule of cocaine (0.66 mg/kg/infusion) and food (45 mg) in 180 min sessions. Once rats could reliably nose-poke for comparable number of reinforcers over sessions, and demonstrate extinction selectively for each reinforcer, pretreatments were examined. The GABAB agonist baclofen (2.5-10.0 mg/kg i.p.) administered 30 min before the start of the session, dose-dependently attenuated behaviour maintained by cocaine, whereas responding maintained by food was marginally decreased. 4,5,6,7-Tetrahydroisoxazolo [5,4-c]pyridin-3-ol hydrochloride (THIP) (2-8 mg/kg i.p.) a GABAA agonist failed to modify cocaine-maintained or food-maintained responding. In another experiment, behaviour maintained by cocaine (0.66 mg/kg/infusion) under an FR-5 TO 20 s schedule of reinforcement was attenuated by intra-nucleus accumbens (100-300 ng) or intra-ventral tegmental area (300 ng) administration of baclofen. Similar doses of baclofen administered into the striatum had no effect. Repeated systemic pretreatment for 3 days with baclofen (2.5 mg/kg i.p.) produced gradual decreases in cocaine-maintained responding. A larger dose (5.0 mg/kg i.p.) tested repeatedly for 5 days decreased the number of cocaine injections self-administered. The present findings demonstrate that modulation of GABA systems may have therapeutic potential for the treatment of psychomotor stimulant abuse.

PMID:
9832934
[PubMed - indexed for MEDLINE]

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