Chronic estrogen treatment replaces striatal dopaminergic function in ovariectomized rats

Eight-week-old female Sprague-Dawley rats were divided into three groups: ovariectomized rats (OVX); ovariectomized rats treated with estradiol valerate (E2), 20 microg subcutaneously (s.c.) twice weekly for 12 weeks (OVX+E2 group); and sham-operated control rats treated with vehicle alone (controls). Spontaneous locomotor activity was measured for 24 h, and then again after the administration of methamphetamine (1 mg/kg, i.p.). In addition, striatal contents of dopamine (DA) and its metabolites were measured. Using an in vivo microdialysis technique, changes in extracellular striatal dopamine concentration were studied in a separate set of similarly treated rats after the administration of methamphetamine (0.2 mg/kg, i.p.). Spontaneous locomotor activity decreased in the OVX group, and estradiol replacement reversed this decreased activity. No significant differences were observed in the contents of DA and its metabolites at the striatum among the three groups. The basal output of DA at the striatum was lower in the OVX group than in those of the other two groups. Extracellular DA concentration following methamphetamine administration was also lower in the rats of OVX group. These results indicate that ovariectomy decreases spontaneous locomotor activity, response to methamphetamine, and striatal DA release in the female rats. Chronic replacement of estrogen reversed spontaneous locomotor activity and DA release by the striatum. These results suggest that chronic administration of estrogen may be beneficial in the treatment of female menopausal patients with Parkinson's disease.