Phenotypes of reinforcement sensitivity as predictors of the response to acute antidepressant treatment in rats

Abstract

One of the biggest threats to modern societies is the increasing prevalence of mood disorders. Cognitive deficits associated with depressive and bipolar disorders are a major driver of functional impairment and the ensuing disability of the suffering individuals. Growing evidence has indicated strong inter-individual differences in the vulnerability to development and effectivity of treatment of these psychiatric conditions, linking various levels of reinforcement sensitivity with specific mood conditions. In this study, we took a unique opportunity to investigate how trait sensitivity to reinforcement determines the reactivity of rats to acute antidepressant treatment.For this, using a preclinical version of the probabilistic reversal-learning (PRL) paradigm, we identified 4 phenotypes of sensitivity to negative and positive feedback in rats, which could represent various types of potential vulnerability to affective disorders. Subsequently, using the light/dark box (LDB) and progressive ratio schedule of reinforcement (PRSR) tests, we evaluated inter-phenotypic differences in the effects of acute treatment with 3 different antidepressant drugs (escitalopram, mirtazapine and clomipramine, each in 3 doses) on anxiety and appetitive motivation of experimental animals.We report statistically significant differences between the investigated phenotypes of reinforcement sensitivity in the effects of acute escitalopram treatment on anxiety in the LDB test. We also report phenotype-independent effects of mirtazapine on motivation and anxiety and a lack of effect of clomipramine.These results demonstrate for the first time that trait sensitivity to reinforcement could have important implications for the effectiveness of treatment in affective disorders.