Sensitivity to negative and positive feedback as a stable and enduring behavioural trait in rats.

RATIONALE: According to psychological theories, cognitive distortions play a pivotal role in the aetiology and recurrence of mood disorders. Although clinical evidence for the coexistence of depression and altered sensitivity to performance feedback is relatively coherent, we still do not know whether increased or decreased sensitivity to positive or negative feedback is associated with 'pro-depressive' profile in healthy subjects. OBJECTIVE: Our research has been designed to answer this question, and here, we present the first steps in that direction. METHODS: Using a rat version of the probabilistic reversal-learning (PRL) paradigm, we evaluated how sensitivity to negative and positive feedback influences other cognitive processes associated with mood disorders, such as motivation in the progressive ratio schedule of reinforcement (PRSR) paradigm, hedonic status in the sucrose preference (SP) test, locomotor and exploratory activity in the open field (OF) test, and anxiety in the light/dark box (LDB) test. RESULTS: The results of our study demonstrated for the first time that in rodents, sensitivity to negative and positive feedback could be considered a stable and enduring behavioural trait. Importantly, we also showed that these traits are independent of each other and that trait sensitivity to positive feedback is associated with cognitive flexibility in the PRL test. The computational modelling results also revealed that in animals classified as sensitive to positive feedback, the α learning rates for both positive and negative reward prediction errors were higher than those in animals classified as insensitive. We observed no statistically significant interactions between sensitivity to negative or positive feedback and the parameters measured in the PRSR, SP, OF or LDB tests. CONCLUSIONS: Further studies using animal models of depression based on chronic stress should reveal whether sensitivity to feedback is a latent trait that when interacts with stressful life events, could produce correlates of depressive symptoms in rats.

Effects of cognitive judgement bias and acute antidepressant treatment on sensitivity to feedback and cognitive flexibility in the rat version of the probabilistic reversal-learning test.

Depressive disorders are often associated with cognitive biases. In this study, we investigated, in an animal model, whether cognitive judgement bias, measured as a stable and enduring behavioural trait, could modulate the effects of antidepressant drugs on other cognitive processes associated with depression. For this purpose, we identified rats displaying 'pessimistic' and 'optimistic' traits in a series of ambiguous-cue interpretation (ACI) tests. Subsequently, in the preclinical version of the probabilistic reversal-learning (PRL) test, allowing multiple reversals within a test session, we compared the effects of acute administration of 5 different antidepressant (AD) drugs (agomelatine, escitalopram, clomipramine, mirtazapine and venlafaxine) on cognitive flexibility and sensitivity to positive/negative feedback in optimistic and pessimistic animals. We report that, following acute treatment with agomelatine, the proportion of lose-shift behaviours in the PRL test was significantly reduced in pessimistic animals compared to optimists. We also demonstrate that acute treatment with another antidepressant drug, mirtazapine, significantly increased the sensitivity of rats to positive feedback, as indexed by the increased proportion of win-stay behaviour following probabilistic reward. This effect was independent of cognitive bias and was associated with a reduced number of reversals made by the animals. Three other tested drugs had no significant effects on behavioural measures assessed in our study.

Using rodents to model abnormal sensitivity to feedback in depression.

Depressive disorder accounts for a substantial proportion of psychiatric problems across the globe and has a devastating impact on quality of life and occupational function. Psychological models of depression emphasize the causal role of cognitive distortions in this disease, and cognitive problems have been included in the diagnostic criteria for depressive episodes. Here, we focus on recent progress in preclinical modelling of aberrations in one of the most important neurocognitive mechanisms involved in the manifestation of depression - abnormal sensitivity to positive and negative feedback. First, we summarize the recent advances in understanding neurocognitive mechanisms of aberrant feedback sensitivity in depression and underlying neurobiological substrates. Second, by combining behavioural, neurochemical, neuroanatomical and pharmacological approaches, we evaluate the translational value of the probabilistic reversal-learning (PRL) task, a behavioural paradigm that enables investigation of correlates of feedback sensitivity in humans and animals. Finally, we identify and discuss directions for future investigation, including cognitive biomarkers of depression and resilience to stress based on feedback sensitivity and personalized treatment targets.

The trait 'pessimism' does not interact with cognitive flexibility but makes rats more vulnerable to stress-induced motivational deficits: Results from the attentional set-shifting task.

In the present study, we have investigated the effects of the traits 'optimism' and 'pessimism' on cognitive flexibility in an animal model of depression based on chronic restraint stress. For this, first, we trained and tested the rats in a series of ambiguous-cue interpretation (ACI) tests, which allowed us to classify them as 'optimistic' or 'pessimistic'. Subsequently, we re-trained and re-tested the animals in the Attentional Set Shifting Task (ASST), which allowed evaluation of the differences between 'optimists' and 'pessimists' in terms of cognitive flexibility. Finally, we subjected half of the 'optimistic' and half of the 'pessimistic' rats to chronic (2 weeks) restraint stress and assessed the interaction between cognitive judgement bias and stress in the ASST. Although we did not observe statistically significant effects of the investigated traits and stress on cognitive flexibility, the 'pessimistic' animals subjected to chronic restraint stress showed significantly longer latencies to approach experimental rewards than their 'optimistic' conspecifics. This effect may indicate a stress-induced motivational deficit that is specific to 'pessimistic' animals. The results of the present study, along with our previous reports, indicate that the trait 'pessimism' determines animals' vulnerability to stress.

Cognitive Judgment Bias Interacts with Risk Based Decision Making and Sensitivity to Dopaminergic Challenge in Male Rats.

Although the cognitive theory has implicated judgment bias in various psychopathologies, its role in decision making under risk remains relatively unexplored. In the present study, we assessed the effects of cognitive judgment bias on risky choices in rats. First, we trained and tested the animals on the rat version of the probability-discounting (PD) task. During discrete trials, the rats chose between two levers; a press on the "small/certain" lever always resulted in the delivery of one reward pellet, whereas a press on the "large/risky" lever resulted in the delivery of four pellets. However, the probability of receiving a reward from the "large/risky" lever gradually decreased over the four trial blocks. Subsequently, the rats were re-trained and evaluated on a series of ambiguous-cue interpretation (ACI) tests, which permitted their classification according to the display of "optimistic" or "pessimistic" traits. Because dopamine (DA) has been implicated in both: risky choices and optimism, in the last experiment, we compared the reactivity of the dopaminergic system in the "optimistic" and "pessimistic" animals using the apomorphine (APO; 2 mg/kg s.c.) sensitivity test. We demonstrated that as risk increased, the proportion of risky lever choices decreased significantly slower in "optimists" compared with "pessimists" and that these differences between the two groups of rats were associated with different levels of dopaminergic system reactivity. Our findings suggest that cognitive judgment bias, risky decision-making and DA are linked, and they provide a foundation for further investigation of the behavioral traits and cognitive processes that influence risky choices in animal models.