The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats

Neuropharmacology. 2007 Jun;52(7):1555-62. doi: 10.1016/j.neuropharm.2007.02.012. Epub 2007 Mar 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Baclofen / pharmacology
  • Baclofen / therapeutic use*
  • Behavior, Addictive / prevention & control*
  • Behavior, Addictive / psychology
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • GABA Agonists / pharmacology
  • GABA Agonists / therapeutic use*
  • Heroin / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Narcotics / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology
  • Self Administration / psychology
  • Time Factors

Substances

  • GABA Agonists
  • Narcotics
  • Heroin
  • Baclofen