Effect of repeated sodium valproate and topiramate administration on mania-like behaviors induced by methylphenidate in mice

Abstract

Novel and effective treatments for mania are needed, and well-validated animal models are important to reach this goal. The psychostimulant-induced hyperactivity is the most frequently animal model of mania used. Although this model is validated pharmacologically using mood stabilizers, data about its predictive validity with negative controls (i.e., drugs that are clinically ineffective in treating mania) are lacking. The present study evaluated the effects of the repeated administration of a clinically effective drug (sodium valproate) and clinically ineffective drug (topiramate) on methylphenidate (MPH)-induced manic-like behaviors in Swiss mice in the behavioral pattern monitor (BPM). Methylphenidate increased locomotor activity and center activity in the BPM. Valproate attenuated the effect of MPH on locomotor and general activity, with no effect on center activity. Topiramate did not affect any MPH-induced manic-like behaviors. Methylphenidate did not change exploratory activity (rearing or nose poking). These results support the predictive validity of MPH-induced hyperactivity for screening antimanic-like drugs.