Effects of pro‐depressant and immunomodulatory drugs on biases in decision‐making in the rat judgement bias task

Studies in human and non‐human species suggest that decision‐making behaviour can be biased by an affective state, also termed an affective bias. To study these behaviours in non‐human species, judgement bias tasks (JBT) have been developed. Animals are trained to associate specific cues (tones) with a positive or negative/less positive outcome. Animals are then presented with intermediate ambiguous cues and affective biases quantified by observing whether animals make more optimistic or more pessimistic choices. Here we use a high versus low reward JBT and test whether pharmacologically distinct compounds, which induce negative biases in learning and memory, have similar effects on decision‐making: tetrabenazine (0.0–1.0 mg/kg), retinoic acid (0.0–10.0 mg/kg), and rimonabant (0.0–10.0 mg/kg). We also tested immunomodulatory compounds: interferon‐α (0–100 units/kg), lipopolysaccharide (0.0–10.0 μg/kg), and corticosterone (0.0–10.0 mg/kg). We observed no specific effects in the JBT with any acute treatment except corticosterone which induced a negative bias. We have previously observed a similar lack of effect with acute but not chronic psychosocial stress and so next tested decision‐making behaviour following chronic interferon‐alpha. Animals developed a negative bias which was sustained even after treatment was ended. These data suggest that decision‐making behaviour in the task is sensitive to chronic but not acute effects of most pro‐depressant drugs or immunomodulators, but the exogenous administration of acute corticosterone induces pessimistic behaviour. This work supports our hypothesis that biases in decision‐making develop over a different temporal scale to those seen with learning and memory which may be relevant in the development and perpetuation of mood disorders. Decision‐making bias in rats, measured using a judgement bias task, is not altered by acute treatments with pro‐depressant or immunomodulatory drugs, but becomes more negative following chronic treatment. The time course of change in decision‐making bias reflects the subjective reporting of changes in depression symptoms in humans treated with these drugs.