Abstract
Aberrant cognition plays a pivotal role in the development and maintenance of depression. One of the most important cognitive distortions associated with depression is aberrant sensitivity to performance feedback. Under clinical conditions, this sensitivity can be measured using the probabilistic reversal learning (PRL) test, which has also been recently implemented in animal studies. Although the evidence for the coexistence of depression and altered feedback sensitivity is relatively coherent, it is unclear whether this sensitivity can influence the effectiveness of antidepressant treatment. In the present research, we investigated how trait sensitivity to negative and positive feedback interacts with the effects of acute antidepressant treatment on hedonic status in rats. We tested a cohort of rats with a series of 10 PRL tests, and based on this screening, we classified each animal as sensitive or insensitive to negative and positive feedback. Subsequently, in the Latin square design, we evaluated the effects of a single administration of two antidepressant drugs (each at three different doses: agomelatine: 5, 10, and 40 mg/kg; mirtazapine 0.5, 1, and 3 mg/kg) on the hedonic status of rats in the sucrose preference tests. There was no statistically significant interaction between trait sensitivity to feedback and the effects of acute antidepressant treatment on hedonic status in rats.
Highlights
A depressive disorder is a serious mental illness characterized by lowered mood and anhedonia
It has been demonstrated that acute administration of several widely prescribed antidepressants changes the affective bias of naïve rats in the affective bias test [citalopram, desipramine, fluoxetine, mirtazapine, venlafaxine, reboxetine, clomipramine and ketamine (Stuart et al, 2013, 2015)], modulate cognitive judgment bias in the ambiguous-cue interpretation (ACI) test [citalopram, desipramine (Rygula et al, 2014; Golebiowska and Rygula, 2017) and reboxetine (Enkel et al, 2010; Anderson et al, 2013)], and alter the sensitivity of rats to performance feedback in the preclinical version of the probabilistic reversal learning (PRL) task [agomelatine, mirtazapine (Drozd et al, 2019), citalopram (Bari et al, 2010) and ketamine (Rychlik et al, 2017)]
Two rats were removed from the analysis due to fluid leakage during the sucrose preference (SP) test
Summary
A depressive disorder is a serious mental illness characterized by lowered mood and anhedonia (i.e., the loss of pleasure; Belzung et al, 2015). It has been proposed that, at a neuropsychological level, antidepressant drugs remediate the negative affective biases and that, contrary to common opinion, these actions occur relatively quickly, even following a single drug administration (Harmer et al, 2009) This induction of a more positive way of processing environmental stimuli (positive bias) leads to cognitive and psychological reconsolidation and wider antidepressant effect. Acute agomelatine treatment reduced the sensitivity of rats to NF, as indexed by the decreased proportion of lose-shift behaviors, while mirtazapine increased the sensitivity of rats to PF, as indexed by the increased proportion of win-stay behaviors This decrease in NF sensitivity and the increased sensitivity to PF were hypothesized to manifest antidepressantinduced, positive, information-processing biases, similar to those reported previously in humans following acute antidepressant treatment (Arnone et al, 2009; Rawlings et al, 2010; Komulainen et al, 2016). The influence of this trait on the effects of acute administration of two antidepressant drugs, namely, mirtazapine and agomelatine (each in three different doses), on the hedonic processing of rats was investigated using sucrose preference (SP) tests
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