In the central nervous system, γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter. Results from both human and animal studies suggest that neuroadaptation in the GABAergic system and pharmacological sensitivity of GABA receptors play important roles in the behavioral and functional neuronal changes associated with ethanol dependence (Crabbe et al., 2006; Follesa et al., 2006). Acute ethanol consumption enhances GABA neurotransmission and inhibits the glutamatergic system (Nevo and Hamon, 1995). The reduction in excitatory effect and the enhancement of inhibitory GABA neurotransmission account for the sedating and dose-dependent depressant effects of ethanol intoxication. However, prolonged ethanol exposure produces neruoadaptation in these neurotransmitter systems, resulting in reduced inhibitory activity of GABA receptors and a sensitization of N-methyl-d-aspartic acid receptors (see reviews by Crews et al., 1996; Davis and Wu, 2001). Sudden cessation of ethanol intake produces a hyperexcitable neuronal state that results in mild withdrawal symptoms just as the “shakes” which, in more severe cases, leads to seizures, delirium, and excitotoxic neuronal death (Tsai and Coyle, 1998).
