The GABA(B) agonist CGP 44532 decreases cocaine self-administration in rats: demonstration using a progressive ratio and a discrete trials procedure

Previous self-administration experiments have shown that baclofen, the prot otypical GABA(B) agonist, produces an apparent attenuation in the reinforci ng effects of cocaine in rats. The present experiments examined the effects of CPG 44532, a novel and highly specific GABA(B) agonist, on cocaine self -administration using two distinctly different procedures. CGP 44532 (0.063 -0.5 mg/kg) produced a dose dependent decrease in break point on a progress ive-ratio (PR) schedule. A low dose of CGP 44532 (0.125 mg/kg) produced an apparent shift of the cocaine dose-response curve to the right. In contrast there was comparatively little effect on food-reinforced responding on the same PR schedule. Using a discrete-trials procedure that engendered a circ adian pattern of self-administration, CPG 44532 (0.063-0.5 mg/kg) produced a dose-dependent suppression of cocaine intake in the 4 h period following treatment. When a concurrently available food reinforced lever was added to the discrete trials paradigm CGP 44532 failed to disrupt responding for fo od at any of the doses tested. Data from the PR and discrete-trials procedu res taken together indicate that CGP 44532 produced a specific decrease in the motivation to self-administer cocaine. (C) 1999 Elsevier Science Ltd. A ll rights reserved.