The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats.
Opiate addiction is a chronic relapsing disorder characterized by high rates of relapse. The gamma-aminobutyric acid GABA(B) receptor agonist baclofen is known to affect the reinforcing effects of several drugs of abuse, including heroin, as well as to decrease cue-maintained responding for heroin, cocaine and nicotine and suppress alcohol deprivation effect in rats. Here we studied the effect of baclofen on the reinstatement of extinguished heroin-seeking behavior triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin (30 microg/kg per infusion) under a continuous reinforcement schedule. Following extinction, the effect of non-contingent non-reinforced primings with heroin, baclofen or heroin/baclofen combination on the resumption of responding was evaluated. Results indicate that heroin priming (0.25mg/kg) promptly reinitiated heroin-seeking behavior, an effect dose-dependently reduced by baclofen at doses (0.625 and 1.25mg/kg) not affecting responding per sè. Importantly, baclofen did not affect locomotion either alone or in combination with heroin, dispelling any doubt as to the eliciting of possible non-specific (motor) effects. The present results show that GABA(B) receptor activation may reduce the propensity to resume drug-induced heroin-seeking behavior thus offering a possible approach in maintaining opiate abstinence.
Spano
Maria Sabrina
MS
Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.
Fattore
Liana
L
Fratta
Walter
W
Fadda
Paola
P
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use*; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000523:psychology; D013997:Time Factors
D018755:GABA Agonists; D009294:Narcotics; D003932:Heroin; D001418:Baclofen