Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of Transient Dopamine Release Events in the Nucleus Accumbens
Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of Transient Dopamine Release Events in the Nucleus Accumbens
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DOI：
10.1124/jpet.117.241802
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发表时间：
2018-01-01
影响因子：
3.5
通讯作者：
Oleson, Erik B.
中科院分区：
文献类型：
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作者：
Schelp, Scott A.;Brodnik, Zachary D.;Oleson, Erik B.
苯二氮卓类药物是常见的抗焦虑药物，在易感人群中构成滥用倾向。虽然已经确定所有滥用药物都会增加大脑多巴胺水平，并且苯二氮卓类药物是GABA（A）受体的变构调节剂，但仍不清楚它们如何改变多巴胺释放。使用体内快速扫描循环伏安法，我们测量了地西泮诱导的多巴胺瞬时释放事件的频率和幅度的变化。我们发现，地西泮同时增加的频率，并降低在清醒和自由活动的大鼠短暂的多巴胺释放事件的振幅。地西泮改变多巴胺释放事件的频率和振幅的时间过程出现分歧，振幅降低的效果比频率增加的效果更短，但两者的发病率相似。我们的结论是，地西泮通过解除对多巴胺神经元的抑制，增加了多巴胺释放事件的频率，但也降低了它们的振幅。我们推测，苯二氮卓类药物的适度滥用倾向是由于它们除了增加多巴胺释放事件的频率外，还能够降低多巴胺释放事件的幅度。
Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in susceptible individuals. Although it is well established that all drugs of abuse increase brain dopamine levels, and benzodiazepines are allosteric modulators of the GABA(A) receptor, it remains unclear how they alter dopamine release. Using in vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the frequency and amplitude of transient dopamine release events. We found that diazepam concurrently increases the frequency and decreases the amplitude of transient dopamine release events in the awake and freely moving rat. The time course during which diazepam altered the frequency and amplitude of dopamine release events diverged, with the decreased amplitude effect being shorter lived than the increase in frequency, but both showing similar rates of onset. We conclude that diazepam increases the frequency of accumbal dopamine release events by disinhibiting dopamine neurons, but also decreases their amplitude. We speculate that the modest abuse liability of benzodiazepines is due to their ability to decrease the amplitude of dopamine release events in addition to increasing their frequency.