Differences in propensity for drinking alcohol are reflected in subunit- and region-specific GABAA receptor levels

Enhacement of GABAA receptor activity within certain discrete brain areas can elicit increased ethanol consumption, supporting a regionally specific role for GABAergic mechanisms in modulating ethanol reinforcement. The present study investigated if Mts, which were in the highest (HES) or lowest (LES) 15th percentile of ethanol self-administration, had different GABA(A) receptor levels. Male Wistar rats (n = 30) were trained to self-administer ethanol for 8 weeks followed by assessment of GABAA receptor mRNAs. In the last operant session the HES rats (4/group) were consuming significantly more ethanol than the LES rats (1.31 + 0.31 g/kg versus 0.02 + 0.02 g/kg; p < 0.001). Significant GABA(A) receptor mRNA differences were found between the groups, which were subunit- and brain region-specific, with higher mRNA levels in the HES rats in the dorsal raphe (alpha 2, alpha 3, gamma 1), medical raphe (alpha 3, alpha 5, beta 1, beta 3, gamma 1), cerebellum (alpha 1, alpha 6, beta 3, gamma 2long) and hippocampus (beta 1, beta 3, gamma 1 and gamma 2long). The elevated cerebellum al mRNA level in the HES rats was confirmed using Western blotting (mean density units + SEM; LES rats 0.460 + 0.005 versus HES Mts 0.610 + 0.006, p = 0.03). These data suggest that the differences in GABA(A) receptors were due either to the different propensities of the groups to consume ethanol or were caused by their differing ethanol exposure.