Chunk #42 — 3 Neural Substrates for the Negative Emotional State Associated with Alcoholism — 3.2 Between-System Neuroadaptations that Contribute to Compulsivity Associated with the Dark Side of Alcoholism
reduced ethanol self-administration in dependent animals during acute withdrawal and during protracted abstinence (Valdez et al. 2002). When administered directly into the central nucleus of the amygdala, a CRF1/CRF2 antagonist blocked ethanol self-administration in ethanol-dependent rats (Funk et al. 2006). Systemic injections of small-molecule CRF1, antagonists also blocked the increased ethanol intake associated with acute withdrawal and protracted abstinence (Gehlert et al. 2007; Funk et al. 2007). These data suggest an important role for CRF, primarily within the central nucleus of the amygdala, in mediating the increased self-administration associated with dependence. Consistent with the sensitization of the withdrawal response associated with repeated alcohol exposure, a CRF antagonist administered during repeated withdrawal also blocked the development of excessive drinking during withdrawal (Roberto et al. 2010).
