The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens
The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens
复制标题
DOI：
10.1046/j.1460-9568.2002.02084.x
复制
发表时间：
2002-07-01
影响因子：
3.4
通讯作者：
Piazza, PV
中科院分区：
文献类型：
--
作者：
Rougé-Pont, F;Mayo, W;Piazza, PV
神经类固醇是类固醇的一个亚类，可以在中枢神经系统中独立于外周来源合成。人类临床研究表明这些激素与抑郁症和产后情绪障碍有关。在啮齿类动物中，异孕酮 (AlloP) 已被证明具有抗焦虑和有益的特性。这些观察结果表明神经类固醇可以与情绪和动机相互作用。然而，这些效应可能的神经基础仍然未知。在本报告中，我们研究了 AlloP 对中脑多巴胺能 (DA) 投射到伏核的活性的作用，伏核被认为是动机和奖励的生物底物之一。这项研究是通过微透析测量自由活动的大鼠伏隔核中多巴胺 (DA) 的细胞外浓度来进行的。我们研究了 AlloP 的直接作用以及该激素对吗啡注射后 DA 反应的影响。 AlloP 剂量依赖性地增加伏隔核中 DA 的释放。此外，这种激素使吗啡的 DA 反应加倍。脑室内注射 AlloP 剂量为 50 和 100 pmol 时观察到了这些效应。这些结果表明 AlloP 对 DA 的刺激作用可以介导神经类固醇的一些行为效应，特别是这些激素与情绪和动机的相互作用。
Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently from peripheral sources. Clinical studies in humans have associated these hormones with depression and postpartum mood disorders. In rodents, allopregnanolone (AlloP) has been shown to have anxiolytic and rewarding properties. These observations suggest that neurosteroids could interact with mood and motivation. However, the possible neural substrates of these effects remain unknown. In this report, we have studied the action of AlloP on the activity of the mesencephalic dopaminergic (DA) projection to the nucleus accumbens, which is considered one of the biological substrates of motivation and reward. This study was conducted by measuring extracellular concentrations of dopamine (DA) in the nucleus accumbens by means of microdialysis in freely moving rats. We studied both the direct effect of AlloP and the influence of this hormone on the DA response to an injection of morphine. AlloP dose-dependently increased the release of DA in the nucleus accumbens. Furthermore, this hormone doubled the DA response to morphine. These effects were observed for AlloP doses of 50 and 100 pmol injected intracerebroventricularly. These results suggest that the stimulatory effect of AlloP on DA could mediate some of the behavioural effects of neurosteroids and, in particular, the interaction of these hormones with mood and motivation.