Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan.
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences.
Behav Pharmacol. 2022 Apr 1;33(2&3):222-229. doi: 10.1097/FBP.0000000000000638.
There are reports regarding the effects of intracellular Ca2+ and synthesis and release of endocannabinoids. The secretion of endocannabinoids depends on the L-type calcium channel. The present study evaluated the involvement of the cannabinoid CB1 receptors in the effect of L-type calcium channel blocker verapamil on passive avoidance learning (PAL) in adult male rats. In this study, we examined the effects of an acute administration of the cannabinoid CB1 receptors antagonist/inverse agonist AM251 following a chronic administration of the Ca2+ channel blocker verapamil on PAL. Male Wistar rats were administered verapamil (10, 25 and 50 mg/kg) or saline intraperitoneally (i.p) daily for 13 days (n = 10/group). After this treatment period, a learning test (acquisition) was performed, and a retrieval test was performed the following day. The results indicated that chronic systemic administration of verapamil (in a dose-dependent manner) impaired memory acquisition and retrieval. Pre-training acute administration of a selective CB1 antagonist/inverse agonist, AM251 (5 mg/kg, i.p.) did not change memory acquisition and retrieval. Co-administration of the verapamil and AM251 significantly reversed verapamil-induced amnesia, suggesting a functional interaction between AM251 and verapamil. The results indicated the interactive effects of cannabinoid CB1 receptors and L-type calcium channel in passive avoidance learning and AM251 can counter the effects of verapamil on memory.
有报道称细胞内 Ca2+和内源性大麻素的合成和释放会产生影响。内源性大麻素的分泌依赖于 L 型钙通道。本研究评估了大麻素 CB1 受体在 L 型钙通道阻滞剂维拉帕米对成年雄性大鼠被动回避学习（PAL）的影响中的作用。在这项研究中，我们研究了急性给予大麻素 CB1 受体拮抗剂/反向激动剂 AM251 后，慢性给予钙通道阻滞剂维拉帕米对 PAL 的影响。雄性 Wistar 大鼠每天腹膜内（i.p）给予维拉帕米（10、25 和 50mg/kg）或生理盐水（n=10/组），共 13 天。经过这段治疗期后，进行学习测试（获得），次日进行检索测试。结果表明，慢性系统给予维拉帕米（呈剂量依赖性）会损害记忆的获得和检索。预先给予选择性 CB1 拮抗剂/反向激动剂 AM251（5mg/kg，i.p）不会改变记忆的获得和检索。维拉帕米和 AM251 的共同给予显著逆转了维拉帕米引起的健忘症，表明 AM251 和维拉帕米之间存在功能相互作用。结果表明，大麻素 CB1 受体和 L 型钙通道在被动回避学习中存在相互作用，AM251 可以抵消维拉帕米对记忆的影响。
