The major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions, and perhaps dopaminergic and noradrenergic influences (e.g. reviewed by Polich and Criado 2006). Glutamatergic neurotransmission and its neuroadaptive changes have been proposed as important molecular determinants of craving and relapse (e.g., Cornish and Kalivas 2000; Tzschentke and Schmidt 2000). In particular, it is suggested that a hyperglutamatergic state mediates, at least in part, alcohol relapse behavior (Tsai and Coyle 1998). Several studies in animal models and human subjects indicate the possible involvement of NMDA (Bachteler and others 2005; Holter and others 2000; Krystal and others 2003) and metabotropic glutamate receptors during alcohol relapse (Bachteler and others 2005; Backstrom and others 2004; Olive and others 2005). Acamprosate, a drug used to prevent relapse in alcoholic patients (Mann and others 2004), is thought to act via suppressing a hyperglutamatergic state in the brain that has been addicted to alcohol (Dahchour and De Witte 2000; Spanagel and Heilig 2005).
