GABAergic modulation of binge-like ethanol intake in C57BL/6J mice

Abstract

GABA receptor systems have long been implicated in alcoholism, and GABAergic drugs have demonstrated efficacy in altering alcohol intake in some rodent models. The present study was designed to assess the effects of baclofen, muscimol, and gaboxadol (THIP) in a variation on a new mouse model of binge-like ethanol intake. Three hours into their dark cycle, male and female C57BL/6J mice were given access to a 20% unsweetened ethanol solution for 2 h each day, for four days. On day five, mice received varying doses of baclofen, muscimol or THIP and were allowed access to 20% ethanol for 60 min. Baclofen dose-dependently increased binge-like ethanol intake, while both muscimol and THIP reduced ethanol intake. Subsequent studies testing the effect of baclofen, muscimol and THIP on water intake using the same procedure revealed that whereas baclofen had no significant effect, muscimol and THIP both reduced the measure. These results add to the growing literature suggesting a role for GABA receptor systems in the modulation of ethanol intake. However, whereas the role of GABA B receptor systems seems selective in the modulation of binge-like ethanol intake, the role for GABA A receptor systems appears to also extend to general fluid intake.