Chronic daily ethanol and withdrawal: 2. Behavioral changes during prolonged abstinence

BACKGROUND: Our previous investigations have suggested that alcohol abuse may induce persistently compromised hypothalamo-pituitary-adrenal (HPA) function, which could increase risk for subsequent alcohol abuse. The apparent similarity of chronic alcohol abuse-induced HPA defects to the compromised HPA functions associated with posttraumatic stress disorder and atypical depression also suggest potential common mechanisms shared with varied neurobehavioral disorders. Accordingly, we have investigated persistent behavioral effects of previous repetitive daily ethanol consumption and withdrawal. METHODS: Male Sprague-Dawley rats received either daily ad libitum chow, ad libitum liquid diet containing ethanol, or pair-fed isocaloric control liquid diet. The ethanol was gradually introduced over 4 weeks, maintained at 5% w/v for four subsequent weeks, and then gradually removed over 1 week. RESULTS: Four weeks after removal of ethanol from the diet, the previously ethanol-consuming rats exhibited greater (p < 0.05) evidence of anxiety in the elevated plus-maze test and in the novel cork-gnawing test, as well as greater (p < 0.05) locomotor response to a novel environment, compared with controls. CONCLUSIONS: These results suggest that repetitive daily alcohol consumption and withdrawal can induce not only persistent defects in HPA function, but also persistent increases in anxiety and behavioral responsiveness to novelty, all consistent with characteristics of abstinent alcoholics as well as with rats that self-administer increased amounts of alcohol and other drugs of abuse. This suggests that alcohol abuse can induce persistent common or interacting changes in neuroendocrine and behavioral responses that may increase risk for subsequent abuse.