Effect of synthetic cannabinoids on spontaneous neuronal activity: Evaluation using Ca²⁺ spiking and multi-electrode arrays

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• 作者：Joseph S. Tauskela ; ^{joe.tauskela@nrc-cnrc.gc.ca" class="auth_mail" title="E-mail the corresponding author} ; Tanya Comas ; Melissa Hewitt ; Amy Aylsworth ; Xigeng Zhao ; Marzia Martina ; Willard J. Costain
• 关键词：AB-PINACA (PubMed CID ; 71301472) ; CP 55 ; 940 (PubMed CID ; 104895) ; HU-210 (PubMed CID ; 9821569) ; JWH-018 (PubMed CID ; 10382701) ; JWH-250 (PubMed CID ; 44397540) ; MAM-2201 ; (PubMed CID ; 66570720) ; rimonabant ; (PubMed CID ; 104850) ; WIN 55 ; 212&ndash ; 2 (PubMed CID ; 5311501) ; XLR-11 ; (PubMed CID ; 57501498)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 September 2016
• 年：2016
• 卷：786
• 期：Complete
• 页码：148-160
• 全文大小：1728 K

文摘

Activation of cannabinoid receptor 1 (CB₁) inhibits synaptic transmission in hippocampal neurons. The goal of this study was to evaluate the ability of benchmark and emerging synthetic cannabinoids to suppress neuronal activity in vitro using two complementary techniques, Ca²⁺ spiking and multi-electrode arrays (MEAs). Neuron culture and fluorescence imaging conditions were extensively optimized to provide maximum sensitivity for detection of suppression of neural activity by cannabinoids. The neuronal Ca²⁺ spiking frequency was significantly suppressed within 10 min by the prototypic aminoalkylindole cannabinoid, WIN 55,212-2 (10 µM). Suppression by WIN 55,212-2 was not improved by pharmacological intervention with signaling pathways known to interfere with CB₁ signaling. The naphthoylindole CB₁ agonist, JWH-018 suppressed Ca²⁺ spiking at a lower concentration (2.5 µM), and the CB₁ antagonist rimonabant (5 µM), reversed this suppression. In the MEA assay, the ability of synthetic CB₁ agonists to suppress spontaneous electrical activity of hippocampal neurons was evaluated over 80 min sessions. All benchmark (WIN 55,212-2, HU-210, CP 55,940 and JWH-018) and emerging synthetic cannabinoids (XLR-11, JWH-250, 5F-PB-22, AB-PINACA and MAM-2201) suppressed neural activity at a concentration of 10 µM; furthermore, several of these compounds also significantly suppressed activity at 1 µM concentrations. Rimonabant partially reversed spiking suppression of 5F-PB-22 and, to a lesser extent, of MAM-2201, supporting CB₁-mediated involvement, although the inactive WIN 55,212-3 also partially suppressed activity. Taken together, synthetic cannabinoid CB₁-mediated suppression of neuronal activity was detected using Ca²⁺ spiking and MEAs.