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

ABSTRACT:

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 ?g·kg^-1 ), corticosterone (10 and 30 mg·kg^-1 ) and IFN-? (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-? (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.

Linked articles

This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

SUBMITTER: Stuart SA 

PROVIDER: S-EPMC5595760 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature