Effects of valproic acid on an animal model of tardive dyskinesia

GABAergic hypofunction in the basal ganglia is stated as an important mechanism underlying the pathophysiology of tardive dyskinesia. the present study investigates the effects of the GABA-mimetic drug valproic acid (VA) on the manifestation of reserpine-induced orofacial movements, an animal model of tardive dyskinesia. Male Wistar rats received two injections of control solution or of 1 mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with 50, 100, or 200 mg/kg VA or control solution and were observed for quantification of orofacial movements and of open-field general activity. the highest dose of VA inhibited the manifestation of reserpine-induced orofacial movements but none of the VA doses modified reserpine-induced decrease in open-field general activity. These results support the potential of VA as an effective pharmacological tool in the treatment of tardive dyskinesia. (C) 2003 Elsevier Science B.V. All rights reserved.UNIFESP, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilUNIFESP, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilWeb of Scienc