Behavioural Neuroscience Laboratory, Mental Health Research Institute, Melbourne, Australia.
Brain Res. 2010 Mar 19;1321:51-9. doi: 10.1016/j.brainres.2009.12.093. Epub 2010 Jan 14.
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.
本研究旨在通过放射配体结合放射自显影技术测量多巴胺转运体（DAT）、多巴胺 D1 和 D2 受体、5-羟色胺转运体（SERT）、5-羟色胺-1A（5-HT1A）和 5-羟色胺-2A（5-HT2A）受体的密度，阐明雌激素对预脉冲抑制（PPI）的多巴胺能和 5-羟色胺能调节的影响。比较了三组雌性 Sprague-Dawley 大鼠：假手术对照、未经处理的卵巢切除（OVX）大鼠和卵巢切除加 17β-雌二醇植入（OVX+E）大鼠。这些组与我们之前的预脉冲抑制（PPI）研究相同，允许比较结果。结果表明，在伏隔核中，OVX 大鼠的 DAT 水平比完整对照组低 44%。雌激素治疗完全逆转了该脑区 OVX 的作用，使其水平与完整对照组相似。与完整对照组相比，OVX 大鼠的伏隔核和尾状核多巴胺 D2 受体密度分别增加了 28%和 25%。雌激素治疗逆转了这种增加，此外，与完整对照大鼠相比，多巴胺 D2 受体水平分别进一步降低了 25%和 20%。各组之间多巴胺 D1 受体、SERT、5-HT1A 受体或 5-HT2A 受体的密度没有差异。这些结果表明雌激素治疗对中枢多巴胺能但不是 5-羟色胺能功能的指标有影响。观察到的变化与这些雌激素治疗方案对药物诱导的 PPI 破坏的影响没有直接重叠，但可能涉及多种影响，即 DAT 和多巴胺 D2 受体密度的变化。这些数据对于我们理解雌激素治疗在精神分裂症中的潜在保护作用也可能是相关的。
