title: Effects of baclofen and raclopride on reinstatement of cocaine self-administration in the rat.
abstract: At present there is no satisfactory treatment against relapse of drug-seeking behavior. Relapse can be modeled in laboratory animals using reinstatement procedures, whereby previously extinguished self-administration for a drug is reinstated by different factors, such as exposure to cues or drug priming. It is thought that activation of gamma-aminobutyric acid (GABA) B receptor complexes could represent a promising approach to pharmacotherapy for diminishing relapse potential with drugs possessing reinforcing properties. The effects of baclofen (a prototypic GABAB receptor agonist) on cue-induced cocaine reinstatement were evaluated in the rat with or without a priming injection of cocaine. The effects of raclopride (an antagonist of dopamine D2 receptors) were also evaluated. Cue-induced reinstatement under vehicle resulted in a significant increase in the number of presses on the active lever, as compared with extinction lever responding. This effect was accentuated in rats receiving a priming injection of cocaine (cocaine-plus-cue-induced reinstatement). Baclofen, at doses without effects on food-motivated operant behavior (2.5 and 5mg/kg i.p.), dose-dependently decreased the number of active lever presses during cue-induced reinstatement. Baclofen had slightly weaker effects on cocaine-plus-cue-induced reinstatement. Raclopride (0.08 and 0.15 mg/kg s.c.) had similar effects against cue-induced reinstatement although it failed to inhibit cocaine-plus-cue-induced reinstatement at the lower dose. Baclofen dose-dependently and selectively decreased reinstatement of cocaine self-administration. The data obtained provide support for the potential anti-craving efficacy of baclofen in the treatment of cocaine drug-seeking.
authors.affiliation: Porsolt SAS, Research laboratory, Z.A. de Glatigné, 53940 Le Genest-Saint-Isle, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Froger-Colléaux
authors.affiliation: Porsolt SAS, Research laboratory, Z.A. de Glatigné, 53940 Le Genest-Saint-Isle, France. Electronic address: vcastagne@porsolt.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castagné
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009042:Motivation / Q000187:drug effects; D020891:Raclopride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D020891:Raclopride; D001418:Baclofen; D003042:Cocaine
keywords: Abuse; Addiction; Baclofen; Reinstatement; Relapse; Self-administration