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首页> 外文期刊>Addiction biology >Addiction‐related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects
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Addiction‐related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects

机译：普瑞巴林与大鼠和人类吗啡的成瘾相关相互作用：加强和抑制效果

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Abstract The gabapentinoid pregabalin is a rapid‐acting anxiolytic and analgesic, possibly suitable in supervised opioid detoxification. However, clinicians have been cautious in using it because of its unknown addictive risk and rising number of mortalities after pregabalin self‐medication in opioid abusers. Here, we studied interactions of pregabalin and morphine on reward functions of the dopamine system in mice and the efficacy of pregabalin on withdrawal in opioid addicts. After the treatment of mice with pregabalin and morphine, we used electrophysiology to study neuroplasticity in midbrain slices, self‐administration and conditioned place preference tests to investigate the rewarding potential of pregabalin and naloxone‐precipitated morphine withdrawal to evaluate opioid withdrawal symptoms. Further, we ran a pilot single‐blind, randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin alone did not induce glutamate receptor neuroplasticity of dopamine neurons in the ventral tegmental area, but pre‐treatment with pregabalin suppressed morphine‐induced neuroplasticity, hyperlocomotion and morphine self‐administration. Pregabalin administration after chronic morphine exposure failed to induce any rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both morphine‐treated mice and opioid addicts and was well tolerated. Intriguingly, pregabalin administration after a low dose of morphine strongly facilitated ventral tegmental area neuroplasticity and led to increased conditioned place preference. Pregabalin appears to have the efficacy to counteract both reinforcing and withdrawal effects of opioids, but it also has a potentiating effect when given to mice with existing opioid levels.
机译：摘要加巴文蛋白普瑞巴林是一种快速作用的抗焦力和镇痛药，可能适用于监督的阿片类药物排毒。然而，由于其在阿片类药物滥用者的普瑞巴林自我药物后，临床医生因其未知的上瘾风险和死亡率上升的死亡率而持谨慎态度。在此，我们研究了普瑞巴林和吗啡的相互作用对小鼠多巴胺体系的奖励功能以及普瑞巴林在阿片类药物成瘾者中戒断的疗效。在用普瑞巴林和吗啡治疗小鼠之后，我们使用电生理学在中脑切片，自我管理和条件下偏好试验中研究神经塑性，以研究普瑞巴林和纳洛酮沉淀的吗啡戒断的奖励潜力，以评估阿片类药物戒断症状。此外，我们运行了一名飞行员单盲，随机，受控试验（34个海洛因成瘾者），评价普瑞巴林在治疗阿片类药物戒断综合征中的疗效和安全性。单独的普雷巴林没有诱导腹侧特子面积的多巴胺神经元的谷氨酸受体神经塑性，但与普瑞巴林抑制的吗啡诱导的神经塑性，高潮和吗啡自我给药预处理。慢性吗啡暴露未能诱导任何有益效果后的普瑞巴林给药。相反，普瑞巴林抑制了吗啡治疗的小鼠和阿片类药物成瘾者的戒断症状，​​并且耐受良好。有趣的是，在低剂量的吗啡的尿萘醛施用后促进的腹侧细胞区域神经塑性，并导致调节的地方偏好增加。普瑞巴林似乎具有抵消阿片类药物的增强和戒断效果的功效，但是当给予具有现有阿片类药物水平的小鼠时也具有增强效果。

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