A temporal threshold for induction of persistent alcohol preference: Behavioral evidence in a rat model of intermittent intoxication

Objective: Development of alcohol dependence is gradual, requires prolonged exposure to alcohol and reflects neuroadaptive processes in the brain. An understanding of these neuroadaptive processes can lead to novel treatment targets. We recently showed that 7 weeks of intermittent alcohol vapor exposure in rats induces a long-lasting increase of voluntary ethanol consumption, accompanied by changes in gene expression patterns in cingulate cortex and amygdala. These findings prompt the question of whether underlying adaptive processes develop gradually over time or whether a temporal threshold exists for this phenotype conversion to occur. We addressed this question by examining the functional consequences of different exposure durations. Method: Male Wistar rats (N = 43) were exposed to alcohol according to the previously published protocol for 2, 4 or 7 weeks. Following 3 weeks of abstinence to eliminate effects of acute withdrawal, subjects were introduced to voluntary alcohol self-administration in a two-bottle free-choice paradigm with continuous access. Results: Rats exposed to alcohol vapor for 7 weeks displayed a marked increase in voluntary ethanol consumption and a dramatic increase in ethanol preference. In rats exposed for shorter periods (2 and 4 weeks), neither ethanol self-administration nor ethanol preference were increased at any time point. Conclusions: These observations support the existence of a temporal threshold for induction of long-lasting changes in voluntary alcohol consumption. The search for underlying molecular processes should be carried out in this context.