In vivo effects of estrogen and 2-hydroxyestradiol on D-2 dopamine receptor agonist affinity states in rat striatum.

Abstract

The administration of estrogen to ovariectomized rats will result in a dopamine receptor hyposensitive phase at 24 hours followed within 48 hours by a hypersensitive phase. In an attempt to characterize further the molecular mechanism(s) which underlie this biphasic response, we studied the effects of estrogen and one of its metabolites (2-hydroxyestradiol) on striatal D-2 dopamine receptor agonist affinity states. Ovariectomized rats were treated daily with estradiol benzoate (EB; 10 micrograms/kg/day) for 3 days and sacrificed 24 hours after the last dose. Additional groups were treated with 2-hydroxyestradiol (2-OHE 2; 3 micrograms/kg/day), EB (100 micrograms/kg/day) or appropriate vehicle for 3 days and sacrificed 72 hours after the last injection. Animals sacrificed during the hyposensitive phase (i.e. 24 hours) displayed a significant decrease in the ratio of high/low agonist affinity states of the striatal D-2 receptor, while animals sacrificed during the EB- or 2-OHE 2-induced hypersensitive phase (i.e. 72 hours) showed no change in the ratio of high/low agonist affinity states.