Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA.
Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA.
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DOI：
10.1016/j.neulet.2013.07.053
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发表时间：
2013-10-25
影响因子：
2.5
通讯作者：
Rusyniak DE
中科院分区：
文献类型：
--
作者：
Zaretsky DV;Zaretskaia MV;Dimicco JA;Durant PJ;Ross CT;Rusyniak DE
3，4-亚甲基二氧基甲基苯丙胺(MDMA)的急性和慢性并发症与下丘脑-垂体-肾上腺(HPA)轴的激活有关。MDMA如何激活HPA轴尚不清楚。众所周知，HPA对应激的反应是通过下丘脑室旁核(PVH)介导的，并涉及5-HT1a(5-HT1a)受体。我们试图确定PVH和5-HT1A受体是否也参与介导HPA对MDMA的反应。大鼠用生理盐水或5-HT1A拮抗剂Way-100635(Way)预处理，然后全身注射MDMA(7.5mgkg)。经WAY处理的动物在MDMA后血浆ACTH浓度显著降低。为了确定PVH中的神经元是否参与，以及它们是否由5-HT1a受体介导，植入针对PVH的引导导管的大鼠被显微注射GABAA受体激动剂Muscimol，ACSF，或途径MDMA。与ACSF相比，微量注射蝇草酚可显著抑制MDMA诱导的血浆ACTH升高(126vs.588pg/ml，P=0.01)。Way没有任何效果。我们的数据表明，PVH中的神经元不依赖于5-HT1A受体，介导对MDMA的ACTH反应。
Acute and chronic complications from the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) are linked to activation of the hypothalamic-pituitary-adrenal (HPA) axis. How MDMA activates the HPA axis is not known. HPA responses to stress are known to be mediated through the paraventricular (PVH) hypothalamus and to involve serotonin-1a (5-HT1A) receptors. We sought to determine if the PVH and 5-HT1A receptors were also involved in mediating HPA responses to MDMA. Rats were pretreated with either saline or a 5-HT1A antagonist, WAY-100635 (WAY), followed by a systemic dose of MDMA (7.5 mg/kg i.v.). Animals pretreated with WAY had significantly lower plasma ACTH concentrations after MDMA. To determine if neurons in the PVH were involved, and if their involvement was mediated by 5-HT1A receptors, rats implanted with guide cannulas targeting the PVH were microinjected with the GABAA receptor agonist muscimol, aCSF, or WAY followed by MDMA. Compared to aCSF microinjections of muscimol significantly attenuated the MDMA-induced rise in plasma ACTH (126 vs. 588 pg/ml, P=<0.01). WAY had no effect. Our data demonstrates that neurons in the PVH, independent of 5-HT1A receptors, mediate ACTH responses to MDMA.
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