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

Abstract

Studies in human and non-human species suggest that decision-making behaviour can be biased by affective state, also termed an affective bias. To study these behaviours in non-human species, judgement bias tasks 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 judgement bias task and test whether pharmacologically distinct compounds, which induce negative biases in learning and memory, have similar effects on decision-making: tetrabenazine (0.0-1.0mg/kg), retinoic acid (0.0-10.0mg/kg) and rimonabant (0.0-10.0mg/kg). We also tested immunomodulatory compounds: interferon- (0-100units/kg), lipopolysaccharide (0.0-10.0g/kg) and corticosterone (0.0-10.0mg/kg). We observed no specific effects in the judgement bias task 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 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. Graphical abstract and textDecision-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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/358655v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@93dd2corg.highwire.dtl.DTLVardef@19d7e41org.highwire.dtl.DTLVardef@cc1ac1org.highwire.dtl.DTLVardef@1f0775c_HPS_FORMAT_FIGEXP M_FIG C_FIG