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The chronobiotic antidepressant, agomelatine, acts via re-entrainment of circadian rhythms. Earlier work has demonstrated late-life anxiety and reduced corticosterone in post-weaning social isolation reared (SIR) rats. Agomelatine was anxiolytic in this model but did not reverse hypocortisolemia. Reduced corticosterone or cortisol (in humans) is well-described in anxiety states, although the anxiolytic-like actions of agomelatine may involve targeting another mechanism. Central oxytocin and vasopressin exert anxiolytic and anxiogenic effects, respectively, and are subject to circadian fluctuation, while also showing sex-dependent differences in response to various challenges.

Social isolation rearing-induced anxiety and response to agomelatine in male and female rats: Role of corticosterone, oxytocin, and vasopressin