Ethanol dependence produces profound neurochemical and morphological changes within the central nervous system that underlie altered motivational and affective behavior (e.g., Koob, 2009b). Behaviors indicative of dependence–like phenotypes include excessive ethanol self-administration (O'Dell, Roberts, Smith, & Koob, 2004; Rimondini, Sommer, & Heilig, 2003; Walker & Koob, 2007), and the development of anxiety- (Valdez et al., 2002) and depressive-like (Walker et al., 2010) states. The removal of these negative states via ethanol consumption is reinforcing (termed negative reinforcement; Koob, 2009a) and this ‘self-medication’ contributes to excessive ethanol consumption and relapse (Heilig & Egli, 2006; Heilig, Egli, Crabbe, & Becker, 2010; Markou, Kosten, & Koob, 1998). The pattern of acquisition concerning dependence-induced escalation of ethanol self-administration during acute withdrawal follows a standard learning curve, in that self-administration steadily increases with each acute withdrawal self-administration session until a plateau is reached and responding stabilizes (e.g., Walker & Koob, 2008).
