The Effect of Estrogen on Dopamine and Serotonin Receptor and Transporter Levels in the Brain: an Autoradiography Study

The aim of the present study was to elucidate the effect of estrogen on dopaminergic and serotonergic regulation of prepulse inhibition (PPI) by measuring its effects on the density of dopamine transporters (DAT), dopamine D(1) and D(2) receptors, serotonin transporters (SERT), serotonin-1A (5-HT(1A)) and 5-HT(2A) receptors using radioligand binding autoradiography. Three groups of female Sprague-Dawley rats were compared: sham-operated controls, untreated ovariectomized (OVX) rats and OVX rats with a 17beta-estradiol implant (OVX+E). These groups were identical to our previous prepulse inhibition (PPI) studies, allowing comparison of the results. Results showed that in the nucleus accumbens, DAT levels were 44% lower in OVX rats than in intact controls. Estrogen treatment completely reversed the effect of OVX in this brain region to levels similar to those in intact controls. Dopamine D(2) receptor density was increased in OVX rats by 28% in the nucleus accumbens and 25% in the caudate nucleus compared to intact controls. Estrogen treatment reversed this increase and, in addition, reduced dopamine D(2) receptor levels by a further 25% and 20%, respectively, compared to intact control rats. There were no differences between the groups with respect to the densities of dopamine D(1) receptors, SERT, 5-HT(1A) receptors or 5-HT(2A) receptors. These results show effects of estrogen treatment on central indices of dopaminergic, but not serotonergic function. The observed changes do not provide a direct overlap with the effects of these estrogen treatment protocols on drug-induced disruptions of PPI, but it is possible that a combination of effects, i.e. on both DAT and dopamine D(2) receptor density, is involved. These data could also be relevant for our understanding of the potential protective effect of estrogen treatment in schizophrenia.