Antagonism of dopamine supersensitivity by estrogen: neurochemical studies in an animal model of tardive dyskinesia.

The withdrawal from chronic haloperidol or estradiol benzoate (EB) treatment results in a behavioral supersensitivity to dopamine agonists in ovariectomized rats. On the other hand, the administration of EB during the withdrawal from haloperidol or the continuous treatment with EB will attenuate or prevent the development of a supersensitivity to dopamine agonists. The enhanced behavioral sensitivity to dopamine agonists is correlated with an increase in 3H-dopamine binding sites in striatal membranes. The administration of EB during the withdrawal from chronic haloperidol treatment or the continuous administration of EB decreases or prevents the proliferation of dopamine binding sites in the striatum that normally orccur upon withdrawal of these two substances. These results indicate that exogenous estrogens may modulate the number of dopamine receptors in the central nervous system and, as such, may decreasse the incidence and/or relieve the symptoms of tardive dyskinesia.