Alcoholism develops following repeated and prolonged episodes of brain exposure to intoxicating levels of alcohol. Accordingly, prolonged brain alcohol exposure in rodents triggers lasting behavioural changes that parallel features of the clinical syndrome, including a persistent escalation of alcohol self-administration (Rimondini et al. 2002; Roberts et al. 2000). Models using repeated cycles of intoxication and withdrawal mimic the course of the clinical condition, and are most effective for inducing escalation of alcohol intake (O’Dell et al. 2004; Rimondini et al. 2002). Alcohol intake in post-dependent animals is sensitive to acamprosate, an approved alcoholism treatment, while alcohol intake of non-dependent rats is unaffected by this medication (Rimondini et al. 2002). Moreover, similar to the clinical condition (Gilman & Hommer, 2008), the post-dependent state is characterized by a persistently up-regulated behavioural sensitivity to stress (Sommer et al. 2008), while basal levels of circulating glucocorticoids are normal (Rimondini et al. 2002). Thus, neuroadaptive processes induced by prolonged exposure to cycles of intoxication and withdrawal parallel those in human alcoholism, and might be informative for human pathophysiology.
