Risperidone resets the circadian clock in mice

Abstract

Risperidone is an atypical antipsychotic that is active at multiple dopamine and serotonin receptor subtypes. Based on its high affinity for serotonin receptors, we predicted that it might reset circadian rhythms in a nocturnal rodent. We report temporally differentiated and differential effects of various doses of risperidone on the voluntary locomotor activity rhythm in the Indian field mice, Mus booduga. Risperidone (0.5 mg/kg) elicited phase delays at phases between CT (circadian time) 12 to CT18 and CT0 to CT3, and phase advances at CT6, CT9 and CT21. However, mice injected at CT6 showed maximum advances (1.299 ± 0.286 h), whereas at CT15 showed maximum delays (−1.514 ± 0.312 h). Increasing the dose beyond 0.5 mg/kg at maximally responsive CTs (CT6 and CT15) resulted in progressively smaller but significant shifts. Thus, 0.5 mg/kg is the optimal dose in this species. The fact that risperidone resets the circadian rhythm in a mammal can be extended to clinical studies and used for optimal adjustment of the circadian rhythm in mental disorders. Conversely, risperidone administration for various treatments must be carefully timed to prevent unwanted phase shifts in patients.