Differences in propensity for drinking alcohol are reflected in subunit- and region-specific GABA(A) receptor levels

Enhacement of GABAA receptor activity within certain discrete brain areas c an elicit increased ethanol consumption, supporting a regionally specific r ole for GABAergic mechanisms in modulating ethanol reinforcement. The prese nt study investigated if Mts, which were in the highest (HES) or lowest (LE S) 15th percentile of ethanol self-administration, had different GABA(A) re ceptor levels. Male Wistar rats (n = 30) were trained to self-administer et hanol for 8 weeks followed by assessment of GABAA receptor mRNAs. In the la st 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 le vels in the HES rats in the dorsal raphe (alpha 2, alpha 3, gamma 1), medic al 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 con firmed 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 d ifferences in GABA(A) receptors were due either to the different propensiti es of the groups to consume ethanol or were caused by their differing ethan ol exposure.