Journal article
GABAB receptor agonist only reduces ethanol drinking in light-drinking mice
Pharmacology, biochemistry and behavior, Vol.102(2), pp.233-240
08/2012
DOI: 10.1016/j.pbb.2012.04.011
PMID: 22579911
Abstract
Baclofen, a GABAB 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 GABAB1 and GABAB2 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, 10weeks), withdrawal (W, 4cycles during 2weeks of 2day-free-choice and 2day-only-water), reexposure (RE, 2weeks), and adulteration of ethanol solutions with quinine (AD, 2weeks). 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 GABAB receptor depends on the precise balance between the GABAB1 and GABAB2 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.
► How to treat mice that have lost their control over ethanol intake? ► Different effect of baclofen depending on ethanol intake profile in mice. ► Baclofen reduces ethanol intake only in light drinkers. ► Baclofen effects are related to different Gabbr1 and Gabbr2 transcription levels.
Details
- Title: Subtitle
- GABAB receptor agonist only reduces ethanol drinking in light-drinking mice
- Creators
- Gustavo Roberto Villas Boas - Universidade Federal do ParanáCamila Gadens Zamboni - Universidade Federal do ParanáMurilo Calvo Peretti - Universidade Federal do ParanáDiego Correia - Universidade Federal do ParanáAndré Veloso Lima Rueda - Universidade de São PauloRosana Camarini - Universidade de São PauloAna Lucia Brunialti-Godard - Universidade Federal de Minas GeraisRoseli Boerngen-Lacerda - Universidade Federal do Paraná
- Resource Type
- Journal article
- Publication Details
- Pharmacology, biochemistry and behavior, Vol.102(2), pp.233-240
- DOI
- 10.1016/j.pbb.2012.04.011
- PMID
- 22579911
- ISSN
- 0091-3057
- eISSN
- 1873-5177
- Publisher
- Elsevier Inc
- Number of pages
- 8
- Language
- English
- Date published
- 08/2012
- Academic Unit
- Radiology
- Record Identifier
- 9985179681802771
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