Anxiolytic-like action of the antidepressant agomelatine (S 20098) after a social defeat requires the integrity of the SCN

Abstract In rats, social defeat by an aggressive opponent induces a state of anxiety, shown by a decrease in time spent on active explorative behaviour, an increase in immobility, a clear decrease in frequency of all active behavioural parameters (enhanced passivity). We tested the hypothesis whether acute or sub-chronic agomelatine would antagonize the negative consequences of a social defeat. As many chronobiological actions of melatonin and its receptor agonist agomelatine require the integrity of the suprachiasmatic nuclei (SCN), we examined whether the anxiolytic-like action of agomelatine 1 day after a social defeat is still present in SCN-lesioned rats. Sub-chronic administration of agomelatine caused a clear reduction of the social defeat induced behavioural consequences. A single agomelatine injection prior to the post-defeat test was less effective and a single melatonin injection was hardly effective. SCN lesion did not affect the anxiety reaction after a social defeat. Thus, sub-chronic agomelatine treatment or a single agomelatine injection reduced a state of anxiety and passivity caused by asocial defeat. The defeat-induced behavioural changes do not depend on the SCN but agomelatine showed its anxiolytic action only in sham-lesioned animals, which indicates that the anxiolytic-like action of agomelatine requires the integrity of the SCN. Mechanisms sustaining this activity are discussed.