Differential effects of clomipramine on depression-like behaviors induced by the chronic social defeat paradigm in tree shrews

Abstract

Background: Anhedonia is a hallmark symptom in major depression that reflects deficits in hedonic capacity and it is also linked to motivation for reward. However, studies of the features of motivation in depressed tree shrews are rather sparse. Aims: The study aimed to investigate the core feature of depression including lack of interest, motivation reduction, and social avoidance in tree shrews. Furthermore, the effects of the treatment using clomipramine on these depression-like behaviors were assessed. Methods: The paradigm of chronic social defeat in tree shrews was used to evaluate the core feature of depression through examining their sucrose preference, break-point for reward, and social interaction. Results: The results showed that social defeat lowered the curves of the sucrose preference and the break-point, as well as decreased social interaction. The results suggested that the subordinate animals exhibited interest loss, motivational reduction, and social avoidance. After oral treatment with clomipramine (50 mg/kg/day) for four weeks, most of the depression-like behaviors were reversed, whereas the motivational reduction was not clearly affected. Notably, the motivational reduction appeared obviously during the first week after the social defeat, and the conventional tricyclic antidepressant clomipramine did not reverse the reduced motivation. Conclusions: These findings imply that motivational variation might be applied as a more sensitive behavioral index in subordinate animals and could furthermore be used to evaluate potential agents as antidepressants.