Withdrawal from chronic alcohol exposure causes long-term alterations in numerous behavioral outcomes. While several of these alterations are believed to contribute significantly to treatment efficacy in human alcoholics, withdrawal-related anxiety makes a significant contribution to relapse in humans (Cohn et al., 2003; Linnoila, 1989; Lucht et al., 2002; Verheul et al., 2005). The neurophysiological mechanisms governing these long-term changes in anxiety-related behaviors are not well understood. Importantly, numerous rodent models of chronic ethanol exposure have long-term changes in anxiety-like behavior during withdrawal as a common characteristic (Borlikova et al., 2006; Breese et al., 2005; Kliethermes, 2005; Lack et al., 2007; Santucci et al., 2008; Valdez et al., 2002; Zhao et al., 2007). The neural circuitry and neurophysiological mechanisms governing anxiety-like behavior in rodents have been relatively well-studied. Importantly, it has recently been demonstrated that these same brain areas appear to mediate increased anxiety following withdrawal from chronic ethanol exposure (Funk and Koob, 2007; Knapp et al., 2007; Lack et al., 2007).
