Estrogen receptor (ER) subtype agonists alter monoamine levels in the female rat brain.

We assessed the effects of subtype-selective ER agonists on monoamine levels in discrete regions of the female rat brain. Ovariectomized (ovx) rats were treated for 4 days with vehicle, 17ß-estradiol (E; 0.05mg/kg), an ERß agonist (C19; 3mg/kg) or an ERα agonist (PPT; 3mg/kg) and samples from brain regions were assessed for monoamines and metabolites. We also assessed effects of ERß modulation on baseline and fenfluramine-induced release of monoamines in hippocampus using microdialysis. In the first study, E and the ERα agonist increased norepinephrine in cortex and all three ER ligands increased it in the ventral hippocampus. Changes in levels of the noradrenergic metabolite, MHPG and the dopaminergic metabolite, DOPAC were noted in brain areas of ER ligand-treated animals. E also increased levels of 5HIAA in three brain areas. In the microdialysis study, there were no differences among groups in baseline levels of monoamines. However, E and the ERß agonist increased levels of the dopaminergic metabolite, HVA following fenfluramine. In summary, activation of the two nuclear ERs with selective agonists affects monoamine and metabolite levels in discrete brain areas, a number of which are known to play key roles in cognitive and affective function.