The GABA-A γ1 subunit was up-regulated in alcoholics in the caudate. Interestingly, GABA-A receptors that contain this subunit are potentiated by neurosteroids (Puia et al., 1993) and ethanol promotes release of endogenous neurosteroids (Biggio et al., 2007) thus enhancing GABA-A currents in neurons. Chronic ethanol administration in rodents significantly increases expression of the γ1 subunit in the cerebral cortex (Devaud et al., 1995) and hippocampus (Cagetti et al., 2003) and a similar increase was recorded in hippocampal post-mortem brain samples from alcoholics (Jin et al., 2011a). Factorial analysis of global GABAergic gene expression in human brains has further identified the α2β1γ1 gene cluster on chromosome 4 as being influenced by chronic alcohol exposure (Enoch et al., 2013). Therefore, increased sensitivity to neurosteroids of GABA-A receptors may be associated with alcoholism.
