THE GABA(B) AGONIST BACLOFEN MODIFIES COCAINE SELF-ADMINISTRATION IN RATS

The present experiments were conducted to examine further the ability of GABAergic compounds to modify the reinforcing effects of cocaine. I n male Sprague-Dawley rats, behaviour was maintained under a fixed-rat io (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, pretreat ments were examined. The GABA(B) agonist baclofen (2.5-10.0 mg/kg i,p, ) administered 30 min before the start of the session, dose-dependentl y attenuated behaviour maintained by cocaine, whereas responding maint ained 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 GABA agonis t failed to modify cocaine-maintained or food-maintained responding. I n another experiment, behaviour maintained by cocaine (0.66 mg/kg/infu sion) under an FR-5 TO 20 s schedule of reinforcement was attenuated b y intra-nucleus accumbens (100-300 ng) or intra-ventral tegmental area (300 ng) administration of baclofen, Similar doses of baclofen admini stered into the striatum had no effect. Repeated systemic pretreatment for 3 days,vith baclofen (2.5 mg/kg i,p,) produced gradual decreases in cocaine-maintained responding. A larger dose (5.0 mg/kg i,p,) teste d repeatedly for 5 days decreased the number of cocaine injections sel f-administered. The present findings demonstrate that modulation of GA BA systems may have therapeutic potential for the treatment of psychom otor stimulant abuse. Behav Pharmacol 1998; 9:195-206 (C) 1998 Lippinc ott-Raven Publishers.