title: Differences in propensity for drinking alcohol are reflected in subunit- and region-specific GABA(A) receptor levels.
abstract: Enhancement of GABA(A) 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 rats, which were in the highest (HES) or lowest (LES) 15th percentile of ethanol self-administration, had different GABA(A) receptor levels. MaleWistar rats (n=30) were trained to self-administer ethanol for 8 weeks followed by assessment of GABA(A) 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 (α2, α3, γ1), medial raphe (α3, α, β1, β3, γ1), cerebellum (α1, α6, β3, γ2long) and hippocampus (β1, β3, γ1 and γ2long). The elevated cerebellum alpha1 mRNA level in the HES rats was confirmed using Western blotting (mean density units +/-SEM; LES rats 0.460 +/-0.005 versus HES rats 0.610 +/- 0.006, p=0.03). These data suggest that the differences in GABA receptors were due either to the different propensities of the groups to consume ethanol or were caused by their differing ethanol exposure.
authors.affiliation: Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Canada. r.tyndale@utoronto.ca
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: D M
authors.initials: DM
authors.lastname: Tomkins