Nevertheless, there is also evidence that the same haplotypic variations in GABRA2 may alter the subjective effects of ethanol ingestion as measured by self-assessment of ethanol-related sensations [20] and mood [21], and studies using α2-subunit mutant mice suggest that alcohol consumption is influenced by the manipulation even at socially relevant concentrations of ethanol [22]. These findings suggest a more direct relationship between ethanol and α2-subunit containing GABAA receptors and may be resolved by considering the role of intermediate neurotransmitters. For example, inhibition of neurosteroid synthesis (which is activated by ethanol) attenuates differences between risk and protective haplotypes [23], suggesting that ethanol may indirectly facilitate transmission at α2-subunit containing receptors by increasing levels of neurosteroids.
