 Alcohol positively allosterically modulates the binding of GABA, enhancing its effect and resulting in inhibition of neurons projecting into the nucleus accumbens, as well as inhibiting NMDA receptors.This combined with desensitization of alpha-2 adrenergic receptors, results in a homeostatic upregulation of these systems in chronic alcohol use.When alcohol use ceases, the unregulated mechanisms result in hyperexcitability of neurons as natural GABAergic systems are down-regulated and excitatory glutamatergic systems are unregulated.