Decreased reward during acute alcohol withdrawal in rats selectively bred for low alcohol drinking

We have previously hypothesized that increased sensitivity to the dysphoric-like or aversive effects of alcohol withdrawal following an initial exposure to alcohol might be associated with a genetic propensity to avoid alcohol. A decrease in brain reward function, as measured by an elevation in intracranial self-stimulation (ICSS) reward threshold, is one of the few methods available to model dysphoric-like or aversive effects of drug withdrawal in rats. We compared brain reward function during withdrawal following an initial exposure to alcohol in alcohol-naïve rats selectively bred for high (HAD1 line) versus low (LAD1 line) voluntary alcohol consumption. Male HAD1 (n=5) and LAD1 (n=6) rats were implanted with unilateral electrodes in the medial forebrain bundle and trained to bar press for delivery of a 100 microA current that varied in frequency from 45 to 200 Hz. Responding for ICSS was generally stable within subjects across multiple experimental sessions on a given day and across several consecutive days prior to alcohol or water administration. ICSS responding was assessed in both rat lines prior to and at 12, 14, 16, 18, 20, and 24 h following a single intragastric infusion of alcohol (4.0 g/kg body weight) or water. Rats of the LAD1 line, but not those of the HAD1 line, exhibited a decrease in brain reward function as evidenced by a decrease in bar-press responding for ICSS and an increase in ICSS stimulation threshold during alcohol withdrawal. The results suggest that rats selectively bred for low alcohol drinking may experience dysphoric-like effects during withdrawal from an initial exposure to alcohol, while rats selectively bred for high alcohol drinking may not.