Effect of alpha lipoic acid on the tardive dyskinesia and oxidative stress induced by haloperidol in rats.

Haloperidol (HAL) is a widely used neuroleptic drug for the treatment of acute and chronic psychosis. Tardive dyskinesia (TD) is a complex hyperkinetic syndrome consisting of choreiform and athetoid movements, which persists for months or years after withdrawal. Increased levels of thiobarbituric acid reactive products are found in the cerebrospinal fluid and plasma of patients treated with neuroleptics, especially those with movement disorders. Alpha lipoic acid (ALA), a natural metabolic antioxidant, is effective in both prevention and treatment of numerous types of neurological disorders. It is proposed to study the effect of ALA on TD induced by HAL and to correlate it with oxidative stress by studying total antioxidant status and lipid peroxidation (LP). HAL (1 mg/kg/i.p.) was used to induce vacuous chewing movements in rats. ALA was suspended in 0.2% carboxy methyl cellulose at a dose of 25, 50 and 100 mg/kg and was administered orally by oral gavage 1 h before HAL on 21st day of treatment. ALA supplementation significantly decreased HAL-induced TD at a dose of 100 mg/kg and catalepsy dose dependently. ALA improved TD and catalepsy by decreasing HAL-induced LP. ALA and its metabolite dihydro lipoic acid protect against HAL-induced TD and catalepsy by scavenging reactive oxygen species and reactive nitrogen species.