Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal
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杏仁核中央小白蛋白中间神经元调节吗啡戒断过程中的消极情感状态和促肾上腺皮质激素释放激素的表达

DOI:
10.1093/ijnp/pyw060
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发表时间:
2016-07
影响因子:
4.8
通讯作者:
Feifei Wang
Feifei Wang
中科院分区:
医学2区
文献类型:
--
作者:
Li Wang;Minjie Shen;Changyou Jiang;Lan Ma;Feifei Wang

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背景:杏仁核中央核(CeA)是介导厌恶情绪的神经回路的重要组成部分。它在戒断期间的负面情感状态中的作用包括阿片能、GABA能和促肾上腺皮质激素释放因子神经传递的变化。然而,人们对 CeA 神经生物学互连性的调节及其对药物依赖者负强化的影响知之甚少。方法:我们进行电生理记录以评估慢性吗啡戒断期间 CeA 中小清蛋白 (PV)+ 中间神经元的膜兴奋性。我们测试了吗啡戒断引起的负面情感状态,例如厌恶(通过条件性场所厌恶评估)、焦虑(通过高架十字迷宫评估)和快感缺乏样行为(通过糖精偏好测试评估),以及通过光遗传学抑制或激活 CeA 中 PV+ 中间神经元来检测促肾上腺皮质激素释放激素 (CRH) 的 mRNA 水平。结果:慢性吗啡戒断增加了 CeA PV+ 中间神经元的放电率。 CeA PV+中间神经元活性的光遗传学抑制减弱了吗啡戒断引起的负面情感状态,如厌恶、焦虑和快感缺乏行为,而直接激活CeA PV+中间神经元可以触发这些负面情感行为。吗啡戒断期间,CeA PV+ 中间神经元的光遗传学抑制显着减弱了 CeA 中升高的 CRH mRNA 水平。结论:慢性吗啡戒断期间,CeA 中 PV+ 中间神经元的活性上调。吗啡戒断过程中PV+中间神经元的激活对于消极情绪的诱导和CeA中CRH mRNA水平的上调至关重要。
Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive.emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and.corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the.CeA and its effects in the negative reinforcement of drug dependents are poorly understood..Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons.in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states,.such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like.(assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via.optogenetic inhibition or activation of PV+ interneurons in the CeA..Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity.of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety,.and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like.behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the.elevated CRH mRNA level in the CeA..Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation.of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation.of CRH mRNA levels in the CeA.
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