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慢性给予大麻二酚对美沙酮诱导的大鼠戒断期认知记忆损伤的神经保护作用。

Neuroprotective effect of chronic administration of cannabidiol during the abstinence period on methamphetamine-induced impairment of recognition memory in the rats.

机构信息

Cellular and Molecular Research Center.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences.

出版信息

Behav Pharmacol. 2020 Jun;31(4):385-396. doi: 10.1097/FBP.0000000000000544.

DOI:10.1097/FBP.0000000000000544
PMID:32032100
Abstract

Neuropsychiatric disorders, such as addiction, are associated with cognitive impairment, including learning and memory deficits. Previous research has demonstrated that the chronic use of methamphetamine (METH) induces long-term cognitive impairment and cannabidiol (CBD), as a neuroprotectant, can reverse spatial memory deficits induced by drug abuse. The study aimed to evaluate the effect of CBD on METH-induced memory impairment in rats chronically exposed to METH (CEM). For the induction of CEM, animals received METH (2 mg/kg, twice/day) for 10 days. Thereafter, the effect of intracerebroventricular (ICV) administration of CBD (32 and 160 nmol) during the (10 days) abstinence period on spatial memory was evaluated using the Y-Maze test, while recognition memory was examined using the novel object recognition (NOR) test. The results revealed a significant increase in the motor activity of METH-treated animals compared with the control group and, after the 10-day abstinence period, motor activity returned to baseline. Notably, the chronic administration of METH had impairing effects on spontaneous alternation performance and recognition memory, which was clearly observed in the NOR test. Additionally, although the ICV administration of CBD (160 nmol) could reverse long-term memory, a lower dose (32 nmol) did not result in any significant increase in exploring the novel object during short-term memory testing. These novel findings suggest that the chronic administration of METH induces memory impairment and presents interesting implications for the potential use of CBD in treating impairment deficits after chronic exposure to psychostimulant drugs such as METH.

摘要

神经精神疾病,如成瘾,与认知障碍有关,包括学习和记忆缺陷。先前的研究表明,慢性使用甲基苯丙胺(METH)会导致长期认知障碍,而大麻二酚(CBD)作为神经保护剂,可以逆转药物滥用引起的空间记忆缺陷。本研究旨在评估 CBD 对慢性暴露于 METH(CEM)的大鼠 METH 诱导的记忆障碍的影响。为了诱导 CEM,动物接受 METH(2mg/kg,每日两次)10 天。此后,通过 Y 迷宫测试评估 ICV 给予 CBD(32 和 160nmol)在(10 天)禁欲期对空间记忆的影响,而通过新物体识别(NOR)测试评估识别记忆。结果显示,与对照组相比,METH 处理动物的运动活性显著增加,并且在 10 天的禁欲期后,运动活性恢复到基线。值得注意的是,慢性给予 METH 对自发交替表现和识别记忆有损害作用,这在 NOR 测试中明显观察到。此外,尽管 ICV 给予 CBD(160nmol)可以逆转长期记忆,但较低剂量(32nmol)在短期记忆测试中对探索新物体没有显著增加。这些新发现表明,慢性给予 METH 会引起记忆障碍,并为 CBD 在治疗慢性暴露于甲基苯丙胺等精神兴奋剂药物后引起的损伤缺陷方面的潜在用途提供了有趣的启示。

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