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. This study has 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 animal’s choices reflect their prior experience. This study 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 lipopolysaccharide (10ug/kg), corticosterone (10, 30mg/kg) and IFN-α (100U/kg) induced a negative affective bias following acute treatment. Tetrabenazine (1mg/kg) also induced a negative bias but no effects were observed with varenicline, carbamazepine or montelukast. Chronic treatment with IFN-α (100U/kg) and retinoic acid (10mg/kg) impaired the formation of a reward-induced positive bias but did not alter sucrose preference test (SPT).

Conclusion 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.