Alcohol alters the expression of genes involved in neurotransmission, specifically those implicated in GABA synthesis and transport across the synaptic cleft. For example, GAD1, SLC6A1, PRAF2, and GPHN were down-regulated in the hippocampus of human alcoholics as well as in cocaine addicts (Enoch et al., 2013; Enoch et al., 2012; Zhou et al., 2011). GAD1 encodes GAD67, the rate-limiting enzyme for the synthesis of GABA (Asada et al., 1996); SLC6A1 encodes the neuronal GABA transporter GAT-1; PRAF2 encodes the protein implicated in the feedback regulation of synaptic transmission (Koomoa et al., 2008); and GPHN encodes gephyrin, a scaffolding protein that anchors GABAA receptors to the postsynaptic skeleton. These findings provide evidence for a coordinated dysregulation of GABA receptor synthesis and transport that could affect synaptic transmission in human alcoholics.
