The GABAB 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. 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.
Shoaib
M
M
Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA.
Swanner
L S
LS
Beyer
C E
CE
Goldberg
S R
SR
Schindler
C W
CW
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000033:anatomy & histology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005108:Extinction, Psychological; D005502:Food; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D007267:Injections; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology
D018765:Dopamine Uptake Inhibitors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D001418:Baclofen; D003042:Cocaine