<br>抑制嘴内侧被盖核可逆转酒精戒断引起的焦虑样行为。,Neuropsychopharmacology

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抑制嘴内侧被盖核可逆转酒精戒断引起的焦虑样行为。
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-05-06 , DOI: 10.1038/s41386-019-0406-8
Elizabeth J Glover _{1,

2} , E Margaret Starr _{1,

2} , Ying Chao ₁ , Thomas C Jhou ₁ , L Judson Chandler _{1,

2}

Affiliation

急性戒酒会引起许多令人不快的症状，这些症状在阻止康复和长期戒酒方面发挥着重要作用。大量研究集中在神经肽系统和杏仁核在调节急性戒断情感症状中所起的作用，但有希望的临床前研究结果尚未成功转化为临床。喙内侧被盖核（RMTg）与恐惧和焦虑有关。此外，RMTg 神经元对中脑多巴胺神经元发挥抑制性控制，中脑多巴胺神经元的活性在急性戒断期间受到抑制。因此，我们假设 RMTg 可能在介导急性戒断症状中发挥作用。使用使大鼠身体依赖乙醇的慢性乙醇蒸气暴露范例，我们观察到戒断诱导的 RMTg 中 cFos 表达的显着增强。伴随着躯体症状的显着增加和通过颅内自我刺激（ICSS）测量的奖励敏感性的降低。两项测量均遵循与 RMTg cFos 表达相似的时间过程，在停止乙醇暴露后 12 小时出现症状严重程度的峰值。在同一时间点，退缩的大鼠中也观察到了焦虑样行为的加剧。 RMTg 抑制对戒断的躯体症状或戒断引起的奖励敏感性变化没有影响，但显着减弱了戒断引起的焦虑样行为。总之，这些数据表明，RMTg 在与急性戒断相关的负面情感状态中发挥着独特的作用，因此可能在恢复早期促进复发的神经生物学机制中发挥着重要作用。

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Inhibition of the rostromedial tegmental nucleus reverses alcohol withdrawal-induced anxiety-like behavior.

Acute withdrawal from alcohol is associated with a number of unpleasant symptoms that play an important role in preventing recovery and long-term abstinence. Considerable research has focused on the role that neuropeptide systems and the amygdala play in mediating affective symptoms of acute withdrawal, but promising preclinical findings have not translated successfully into the clinic. The rostromedial tegmental nucleus (RMTg) has been implicated in both fear and anxiety. In addition, RMTg neurons exert inhibitory control over midbrain dopamine neurons, the activity of which are suppressed during acute withdrawal. Thus, we hypothesized that the RMTg may play a role in mediating symptoms of acute withdrawal. Using a chronic ethanol vapor exposure paradigm that renders rats physically dependent on ethanol, we observed significant withdrawal-induced enhancement of cFos expression in the RMTg. This was accompanied by a significant increase in somatic symptoms and a decrease in reward sensitivity as measured by intracranial self-stimulation (ICSS). Both measures followed a similar time course to RMTg cFos expression with peak symptom severity occurring 12 h following cessation of ethanol exposure. Heightened anxiety-like behavior was also observed in withdrawn rats at this same time point. RMTg inhibition had no effect on somatic signs of withdrawal or withdrawal-induced changes in reward sensitivity, but significantly attenuated withdrawal-induced anxiety-like behavior. Together, these data demonstrate that the RMTg plays a distinct role in the negative affective state associated with acute withdrawal and may therefore be critically involved in the neurobiological mechanisms that promote relapse during early stages of recovery.

更新日期：2019-05-16

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