and blocked excessive alcohol self-administration in Wistar rats with a history of dependence (Gehlert et al. 2007). CRF also contributes to increased alcohol consumption in dependent animals, because increased EtOH self-administration is reduced by CRF1R antagonists in dependent animals but not in non-dependent animals (Funk et al. 2007; Overstreet et al. 2004) and by CRF1R deletion (Chu et al. 2007; Sillaber et al. 2002). More recently, it has been reported that chronic CRF1R antagonist treatment blocked withdrawal-induced increases in alcohol drinking by dependent rats, and tempered moderate increases in alcohol consumption (Roberto et al. 2010). These results have led to the hypothesis that negative emotional states (including anxiety-like states) contribute to the compulsive alcohol intake associated with dependence via negative reinforcement mechanisms (Koob 2008).
