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

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Science

Background:

• Predicting drug-induced psychiatric adverse effects is crucial but challenging in non-human models.
• Current preclinical methods lack translational and predictive validity for psychiatric drug effects.

Purpose of the Study:

• To evaluate the affective bias test (ABT) as a preclinical method for predicting drug-induced psychiatric effects.
• To assess the translational and predictive validity of the ABT in non-human species.

Main Methods:

• The ABT quantifies biases in learning and memory using a bowl-digging task.
• Rats underwent independent learning experiences with acute drug treatments or varying reward values.
• Affective bias formation and reward-induced positive bias were assessed after acute or chronic drug administration.

Main Results:

• Acute treatment with LPS, corticosterone, and IFN-α induced a negative affective bias.
• Tetrabenazine also induced a negative bias; varenicline, carbamazepine, and montelukast did not.
• Chronic IFN-α and retinoic acid impaired reward-induced positive bias formation without affecting sucrose preference.

Conclusions:

• The ABT offers a novel preclinical approach to predict pro-depressant drug risk.
• Acute negative biases in the ABT may predict chronic reward processing deficits, distinct from anhedonia.