Modulation of dopamine receptor sensitivity by estrogen.

Postmenopausal females have the highest incidence of tardive dyskinesia, suggesting that loss of ovarian function may predispose them to this condition. Moreover, reports have indicated that estrogens could reduce abnormal movements in tardive dyskinesia. To test the effects of estrogen in an animal model of tardive dyskinesia, ovariectomized rats were treated daily for 16 days with haloperidol (Haldol, 0.5 mg/kg) or Haldol + estradiol benzoate (EB, 10 micrograms/kg). Rats were then challenged with d-amphetamine or apomorphine 1 week following cessation of the chronic treatments. Chronic treatments with either Haldol or EB alone produced an enhanced response to both d-amphetamine and apomorphine, while the combined treatment produced a synergistic response. Rats treated chronically with Holdol, and treated daily with EB following the Haldol treatment, showed an attenuation of drug-induced stereotypy. These preliminary data indicate that estrogen can attenuate the development or mask the display of the supersensitive dopamine receptor.