Immediate and lasting effects of chronic daily methamphetamine exposure on activation of cells in hypothalamic-pituitary-adrenal axis-associated brain regions.
Immediate and lasting effects of chronic daily methamphetamine exposure on activation of cells in hypothalamic-pituitary-adrenal axis-associated brain regions.
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DOI：
10.1007/s00213-015-4114-8
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发表时间：
2016-02
影响因子：
3.4
通讯作者：
Raber J
中科院分区：
文献类型：
--
作者：
Zuloaga DG;Johnson LA;Weber S;Raber J
长期滥用甲基苯丙胺会导致依赖性和停止使用后的戒断症状。与戒断相关的负面情绪状态以及药物复吸与药物诱导的下丘脑-垂体-肾上腺（HPA）轴破坏有关。然而，慢性MA暴露或急性MA暴露后退出对大脑区域内的神经激活模式，调节HPA轴的影响是未知的。在本研究中，通过定量暴露于不同MA给药方案的小鼠中的c-Fos蛋白来评估神经激活模式。（实验1）成年雄性小鼠用MA（5 mg/kg）或盐水处理一次或每天一次，持续10天。（实验2）小鼠每天一次接受MA或盐水治疗，持续10天，并在10天的停药期后重新给予最后一剂MA或盐水。在最后一次注射后定量脑中的c-Fos。（实验1）与暴露于单剂量MA（5 mg/kg）相比，慢性MA暴露减少了室旁下丘脑、背内侧下丘脑、中央杏仁核、基底外侧杏仁核、终纹床核（BNST）和CA 3海马区中的c-Fos表达细胞的数量。（实验2）与接受其第一剂量的MA的小鼠相比，用MA长期处理、撤回和再施用MA的小鼠显示中央和基底外侧杏仁核、BNST和CA 3内的c-Fos表达细胞减少。HPA轴相关的杏仁核，杏仁核延长，海马区持久的影响后，慢性MA暴露，因此可能与压力相关的戒断症状。
Chronic methamphetamine (MA) abuse leads to dependence and symptoms of withdrawal after use has ceased. Negative mood states associated with withdrawal, as well as drug reinstatement, have been linked to drug-induced disruption of the hypothalamic-pituitary-adrenal (HPA) axis. However, effects of chronic MA exposure or acute MA exposure following withdrawal on neural activation patterns within brain regions that regulate the HPA axis are unknown. In this study, neural activation patterns were assessed by quantification of c-Fos protein in mice exposed to different regimens of MA administration. (Experiment 1) Adult male mice were treated with MA (5 mg/kg) or saline once or once daily for 10 days. (Experiment 2) Mice were treated with MA or saline once daily for 10 days and following a 10-day withdrawal period were re-administered a final dose of MA or saline. c-Fos was quantified in brains after the final injection. (Experiment 1) Compared to exposure to a single dose of MA (5 mg/kg), chronic MA exposure decreased the number of c-Fos expressing cells in the paraventricular hypothalamus, dorsomedial hypothalamus, central amygdala, basolateral amygdala, bed nucleus of the stria terminalis (BNST), and CA3 hippocampal region. (Experiment 2) Compared to mice receiving their first dose of MA, mice chronically treated with MA, withdrawn, and re-administered MA, showed decreased c-Fos expressing cells within the central and basolateral amygdala, BNST, and CA3. HPA axis-associated amygdala, extended amygdala, and hippocampal regions endure lasting effects following chronic MA exposure and therefore may be linked to stress-related withdrawal symptoms.