title: Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.
abstract: Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P < 0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Division of Behavioral Biology, Johns Hopkins University School of Medicine, Suite, Baltimore, MD, USA.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Duke
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kaminski
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000517:prevention & control; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects*; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010215:Papio; D012055:Reinforcement Schedule; D055502:Secondary Prevention; D012646:Self Administration / Q000706:statistics & numerical data
chemical_list: D058786:GABA-B Receptor Agonists; D000431:Ethanol; D001418:Baclofen