Research ReportsThe interactive effects of verapamil and CB1 cannabinoid receptor antagonist/inverse agonist, AM251 on passive avoidance learning and memory in ratKarimi, Seyed Asaada,b; Noorbakhsh, Mariama; Komaki, Hamidrezaa; Reza Nikoo, Mohammadc; Hasanein, Parisad; Shahidi, Siamaka,b; Faraji, Nafiseha; Komaki, Alirezaa,b Author Information aNeurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan bDepartment of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences cDepartment of Occupational Therapy, School of Rehabilitation Sciences, Hamedan University of Medical Sciences, Hamedan dDepartment of Biology, School of Basic Sciences, University of Zabol, Zabol, Iran Received 28 February 2021 Accepted as revised 22 April 2021 Correspondence to Alireza Komaki, PhD, Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan 65178/518, Iran Tel: +98 81 38380267; fax: +98 81 38380131; e-mail: [email protected] Behavioural Pharmacology: April 2022 - Volume 33 - Issue 2&3 - p 222-229 doi: 10.1097/FBP.0000000000000638 Buy Metrics Abstract 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. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.