title: GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice.
abstract: Baclofen, a GABA(B) agonist, reduces ethanol intake in animals and humans, but the contrary or no effect was also reported. Our previous study demonstrated that mice characterized as "loss of control over ethanol intake" had different Gabbr1 and Gabbr2 transcription levels, which express, respectively, the GABA(B1) and GABA(B2) subunits in brain areas related to addictive behavior. In the present study, we tested baclofen on ethanol intake in mice exposed to the free-choice paradigm. Adult male Swiss mice, individually housed, had free access to three bottles: ethanol (5% and 10%) and water. The protocol had four phases: acquisition (AC, 10 weeks), withdrawal (W, 4 cycles during 2 weeks of 2 day-free-choice and 2 day-only-water), reexposure (RE, 2 weeks), and adulteration of ethanol solutions with quinine (AD, 2 weeks). Mice characterized as "loss of control" (A, n=11, preference for ethanol in AC and maintenance of ethanol intake levels in AD), heavy (H, n=11, preference for ethanol in AC and reduction of ethanol intake levels in AD), and light (L, n=16, preference for water in all phases) drinkers were randomly distributed into two subgroups receiving either intraperitoneal injections of all doses of baclofen (1.25, 2.5, and 5.0mg/kg, given each dose twice in consecutive days) or saline, being exposed to free-choice. Fluid consumption was measured 24h later. Baclofen reduced ethanol intake in group L. In group H a reduction compared to AC was observed. Group A maintained their high ethanol intake even after baclofen treatment. Activation of the GABA(B) receptor depends on the precise balance between the GABA(B1) and GABA(B2) subunits, so the disproportionate transcription levels, we reported in group A, could explain this lack of response to baclofen. These data highlight the importance to test baclofen in individuals with different ethanol drinking profiles, including humans.
authors.affiliation: Departmento de Farmacologia, Universidade Federal do Paraná, Jardim das Américas, Curitiba, Paraná 81531-990, Brazil.
authors.forename: Gustavo Roberto
authors.initials: GR
authors.lastname: Villas Boas
authors.forename: Camila Gadens
authors.initials: CG
authors.lastname: Zamboni
authors.forename: Murilo Calvo
authors.initials: MC
authors.lastname: Peretti
authors.forename: Diego
authors.initials: D
authors.lastname: Correia
authors.forename: André Veloso Lima
authors.initials: AV
authors.lastname: Rueda
authors.forename: Rosana
authors.initials: R
authors.lastname: Camarini
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Brunialti-Godard
authors.forename: Roseli
authors.initials: R
authors.lastname: Boerngen-Lacerda
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior; D000431:Ethanol / Q000008:administration & dosage*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018080:Receptors, GABA-B / Q000187:drug effects*
chemical_list: D018755:GABA Agonists; D018080:Receptors, GABA-B; D000431:Ethanol; D001418:Baclofen