Using the affective bias test to predict drug-induced negative affect: implications for drug safety

BACKGROUND AND PURPOSE Predicting the risk of drug-induced adverse psychiatric effects is important but currently not possible in non-human species. We investigated whether the affective bias test (ABT) could provide a preclinical method with translational and predictive validity. EXPERIMENTAL APPROACH The ABT is a bowl-digging task, which quantifies biases associated with learning and memory. Rats encounter independent learning experiences, on separate days, under either acute manipulations (e.g. pro-depressant vs. control) or different absolute reward values (e.g. high vs. low). A bias is observed during a preference test when an animal's choices reflect their prior experience. We investigated the effects of putative pro-depressant drug treatments following acute or chronic administration on the formation of an affective bias or reward-induced positive bias respectively. KEY RESULTS The immunomodulators LPS (10 mu g.kg(-1)), corticosterone (10 and 30 mg.kg(-1)) and IFN-alpha (100 U.kg(-1)) induced a negative affective bias following acute treatment. Tetrabenazine (1 mg.kg(-1)) also induced a negative bias, but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-a (100 U.kg(-1)) and retinoic acid (10 mg.kg(-1)) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT). CONCLUSIONS AND IMPLICATIONS The ABT has the potential to provide a novel approach to predict pro-depressant risk in a non-human species. Negative biases induced by acute treatment in the standard version of the task may also predict longer-term effects on reward processing as shown by the deficit in reward-induced positive bias following chronic treatment, an effect distinct from anhedonia in the SPT.