Similar effect of estradiol and haloperidol on experimental tardive dyskinesia in monkeys

In a group of ovariectomized monkeys, a persistent buccolingual dyskinesia resembling tardive dyskinesia was induced by an upper midbrain lesion. This dyskinesia was increased by apomorphine. A single dose of haloperidol (1 mg/kg) reduced the effect of apomorphine after 24 hours and caused an increase in CSF homovanillic acid. Fifteen days later, however, the response to apomorphine was markedly enhanced. Estradiol benzoate (0.5 mg sc) had a similar biphasic effect, although of lesser magnitude. In a different group of lesioned but non-dyskinetic animals, the CSF concentration of HVA also was elevated 24 hours after estradiol. These results support our hypothesis that estradiol shares several properties with neuroleptics, and in particular, reduces, then enhances the sensitivity of striatal dopaminergic receptors.