Abstract
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 (0.0-1.0mg/kg), retinoic acid (0.0-10.0mg/kg), and rimonabant (0.0-10.0mg/kg). We also tested immunomodulatory compounds: interferon-α (0-100units/kg), lipopolysaccharide (0.0-10.0μg/kg), and corticosterone (0.0-10.0mg/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.
Highlights
Affective biases, when emotions alter cognitive processing, occur across many different cognitive domains
Studies have demonstrated that negative affective biases in processes such as emotional interpretation, learning, memory, and decision- making contribute to the development and maintenance of mood disorders such as depression and anxiety (Mathews & MacLeod, 2005; Leppänen, 2006; Elliott et al, 2011; Roiser et al, 2012; Robinson & Roiser, 2016)
These findings support earlier hypotheses relating to the role of neuropsychological processes in major depressive disorder (MDD) (Beck, 1967, 1976), and adds to the proposal that negative affective biases have a causal role in the development, maintenance, and treatment of MDD (Clark et al, 2009; Harmer et al, 2009; Robinson & Sahakian, 2008)
Summary
Affective biases, when emotions alter cognitive processing, occur across many different cognitive domains. Other NMDA receptor antagonists that have not shown clinical antidepressant efficacy (phencyclidine [PCP], lanicemine, and memantine) fail to induce a change in bias when given acutely (Hales et al, 2017, 2020) These data suggest that this reward-based JBT is sensitive to pharmacological treatments that induce biases across time courses that correspond to subjectively reported changes in mood in humans following these drug treatments. Another rodent task that measures affective biases in learning and memory, the affective bias test (ABT; Stuart et al, 2013), is sensitive to acute changes induced by conventional antidepressants, as in humans (Harmer et al, 2017). In previous studies using psychosocial stress, we observed negative decision- making biases in the JBT following chronic but not acute exposure (Hales et al, 2016), here we tested IFN-α effects following chronic treatment
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