Allopregnanolone increase in striatal N-Methyl-D-aspartic acid evoked [3H]dopamine release is estrogen and progesterone dependent
Allopregnanolone increase in striatal N-Methyl-D-aspartic acid evoked [3H]dopamine release is estrogen and progesterone dependent
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DOI：
10.1023/a:1021015705597
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发表时间：
2002-08-01
影响因子：
4
通讯作者：
Mampel, A
中科院分区：
文献类型：
--
作者：
Cabrera, RJ;Bregonzio, C;Mampel, A
1.神经类固醇是由类固醇激素衍生并在神经系统中合成的化合物。它们可以调节不同的神经递质通路。在以前的工作中，我们证明了孕酮调节多巴胺能激动剂N-甲基-D-天冬氨酸（NMDA）诱导的多巴胺释放。这项工作的目的是评估可能的调节作用的孕酮代谢物allopregnanolone对NMDA诱发的[H-3]多巴胺释放从纹状体切片获得骑自行车和卵巢切除的雌性大鼠。我们使用动态灌流方法来评估[3 H]多巴胺的释放。将50-600 nM的别孕烯醇酮加入到灌流缓冲液（Krebs Ringer碳酸氢盐葡萄糖，pH 7.4，具有恒定的O-2/CO2充气）中。结果表示为相对于由组织负载的基础[H-3]多巴胺的百分比。Allopregnanolone（50和100 nM）增加了NMDA诱发的[H-3]多巴胺从发情大鼠的释放。其余剂量未显示释放模式的显著变化。在间情期大鼠中未观察到这种效应。卵巢切除取消了别孕烯醇酮对NMDA诱发的2 [H-3]多巴胺释放的易化作用.皮下注射外源性雌激素（25 mg/只）和孕激素（1 mg/只）可恢复多巴胺能输入的易化作用.这些结果表明，allopregnanolone是一种神经甾体能够调节多巴胺释放的卵巢激素波动依赖性的方式，并提供进一步的支持allopregnanolone的作用，作为一个调制器的多巴胺能相互作用在纹状体。
1. The neurosteroids are compounds derived from steroid hormones and synthesized in the nervous system. They can modulate different neurotransmitter pathways. In previous work we demonstrated that progesterone modulates dopamine release induced by the glutamatergic agonist N-methyl-D-aspartic acid (NMDA).2. The aim of this work was to evaluate a possible modulatory role of the progesterone metabolite allopregnanolone on NMDA-evoked [H-3]dopamine release from corpus striatum slices obtained from cycling and ovariectomized female rats.3. We used a dynamic superfusion method to evaluate the release of [3H]dopamine. Allopregnanolone at 50-600 nM was added to the superfusion buffer (Krebs Ringer bicarbonate glucose, pH 7.4, with constant O-2/CO2 gassing). The results are expressed as a percentage over basal [H-3]dopamine loaded by the tissue.4. Allopregnanolone (50 and 100 nM) increased the NMDA-evoked[H-3]dopamine release from estrus rats. The remaining doses did not show significant changes in the pattern of release. This effect was not observed in diestrus rats. The ovariectomy abolished the facilitatory effect of allopregnanolone on NMDA-evoked 2 [H-3]dopamine release.5. Subcutaneous administration of exogenous estrogen (25 mg/rat) and progesterone (1 mg/rat) restored the facilitatory effect on dopaminergic input.6. These results suggest that allopregnanolone is a neurosteroid able to modulate dopamine release in an ovarian-hormone-fluctuation-dependent manner and provide further support for a role of allopregnanolone as a modulator of glutamatergic-dopaminergic interaction in the corpus striatum.