Background and Purpose: Currently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats. Experimental Approach: Here we tested whether administration of 2.5 mg·kg^-1 diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg·kg^-1 cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity. Key Results: Cocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%. Conclusions and implication: These results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam. What is already known: Diazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine. What this study adds: Diazepam attenuated the increase in phasic dopamine release caused by cocaine. Diazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity. Clinical significance: This study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction.

中文翻译：

---

地西p减弱可卡因对大鼠伏伏核运动，50 kHz超声发声和多巴胺释放的影响

背景与目的：目前，尚无有效的药物可治疗可卡因使用失调症，该病可影响全球数百万人。苯二氮卓类药物是潜在的治疗候选药物，因为微透析和伏安法研究表明它们可以减少啮齿动物伏隔核中多巴胺的释放。此外，我们最近发现地西epa可阻止多巴胺释放和由DL-苯异丙胺诱导的情感标记50 kHz超声发声（USV）。实验方法：在这里我们测试了在成年雄性Wistar大鼠中施用2.5 mg·kg ^-1地西epa（ip）是否可以阻断20 mg·kg ^-1的作用可卡因（ip）通过快速扫描循环伏安法测量伏安核中电诱发的相位多巴胺释放以及50 kHz USV和运动活性。关键结果：可卡因注射可使诱发的多巴胺释放在5分钟内增加多达3倍，并且至少在90分钟内明显高于基线。15分钟后注射地西epa使可卡因作用减弱了近50％，并且这种衰减至少维持了30分钟。已知刺激性药物，自然奖励和奖励预测提示会在成年大鼠中诱发50 kHz USV。在本研究中，可卡因将平面，阶跃，颤音和混合形式的50kHz USV数量增加了12倍。这种作用在可卡因注射后最多5分钟，随时间下降并持续至少40分钟。地西p在整个疗程中均显着阻断了这种作用。在开阔的田野中进行探索40分钟的过程中，对照大鼠所经过的距离在开始的5分钟内最大，并且逐渐衰减直至会议结束。与对照组相比，可卡因治疗的大鼠行进的距离明显更长，而地西epa显着降低了可卡因诱导的运动，最多可降低50％。结论和意义：这些结果表明，地西epa可以减轻可卡因的神经化学，情感和刺激作用。已知：地西p减少了啮齿动物伏隔核（NAc）中的多巴胺释放，并降低了DL-苯异丙胺产生的某些作用。该研究的补充内容：地西p减轻了可卡因引起的多巴胺释放的增加。地西p阻断了可卡因对50kHz USV和运动活性的作用。临床意义：这项研究表明地西epa可以阻断可卡因的特殊作用，而这种作用可能会导致成瘾。