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Discriminative stimulus and reinforcing effects of diclazepam in rodents
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2023-11-26 , DOI: 10.1016/j.pbb.2023.173687
Wonjong Lee 1 , Jung Won Lee 2 , Sungsun Kim 1 , Jin Mook Kim 1 , Dong-Hyun Youn 1 , Seong Hye Park 1 , Chan Hyeok Kwon 1 , Sun-Ok Choi 1
Affiliation  

Diclazepam, a designer benzodiazepine, is a lesser-known novel anxiolytic substance and a structural analog of diazepam. Although several case studies have reported the adverse effects of diclazepam, their potential impacts remain unknown. Therefore, this study aimed to determine the effects of diclazepam in rodents using drug discrimination, locomotor activity, self-administration (SA), and conditioned place preference (CPP) tests. Sprague-Dawley rats (male, 8 weeks old, weighing 220–450 g, n = 12 per group) and C57BL/6 mice (male, 7 weeks old, weighing 20–25 g, n = 7–8 per group) were administered alprazolam, morphine, and diclazepam. Diclazepam fully elicited alprazolam-appropriate dose-dependent lever responses (>80 %) similar to those of alprazolam. In rats administered 0.5 mg/kg of morphine, a partial substitution (80 %–20 %) was observed. Mice receiving intraperitoneal injections of diclazepam (0.05, 0.2, and 2 mg/kg) showed decreased locomotor activity. In the SA experiment, mice that self-administered intravenous diclazepam (2 μg/kg/infusion) showed significantly higher infusion and active lever responses compared to the vehicle group. No statistically significant rewarding effects of diclazepam at the doses of 0.2 and 2 mg/kg evaluated using the CPP paradigm were found. In conclusion, diclazepam has reinforcing effects and shares the interoceptive effects of alprazolam. Therefore, legal restrictions on the use of diclazepam should be carefully considered.



中文翻译:

地氯西泮对啮齿类动物的辨别刺激和强化作用

地西泮是一种苯二氮卓类药物,是一种鲜为人知的新型抗焦虑物质,是地西泮的结构类似物。尽管一些案例研究报告了地氯西泮的不良反应,但其潜在影响仍然未知。因此,本研究旨在通过药物辨别、运动活动、自我给药(SA)和条件性位置偏好(CPP)测试来确定地克西泮对啮齿类动物的影响。Sprague-Dawley 大鼠(雄性,8 周龄,体重 220-450 g,每组 n = 12 只)和 C57BL/6 小鼠(雄性,7 周龄,体重 20-25 g,每组 n = 7-8 只)给予阿普唑仑、吗啡和地克西泮。与阿普唑仑相似,地克西泮完全引起阿普唑仑适当的剂量依赖性杠杆反应(>80%)。在给予 0.5 mg/kg 吗啡的大鼠中,观察到部分替代(80%–20%)。接受腹腔注射地克西泮(0.05、0.2 和 2 mg/kg)的小鼠表现出运动活性下降。在 SA 实验中,与媒介物组相比,自行静脉注射地克西泮(2 μg/kg/输注)的小鼠表现出显着更高的输注和主动杠杆反应。使用 CPP 范式评估的 0.2 和 2 mg/kg 剂量的地氯西泮没有发现统计学上显着的奖励效应。总之,地氯西泮具有增强作用,并具有阿普唑仑的内感受作用。因此,应仔细考虑对地氯西泮使用的法律限制。

更新日期:2023-11-26
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