Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Neurochem Res. 2022 Sep;47(9):2899-2908. doi: 10.1007/s11064-022-03708-8. Epub 2022 Aug 19.
The number of cannabis users is increasing in the world. However, the mechanisms involved in the psychiatric effects and addiction formation remain unclear. Medical treatments against cannabis addiction have not yet been established. Δ9-Tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were intraperitoneally (i.p.) administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments on anxiety and addiction were performed. Administration of ACPA caused anxiolytic-like behavior in the elevated plus maze test. In addition, ACPA increased place preference in a conditioned place preference (CPP) test. The basolateral amygdala (BLA), which is the focus of this study, is involved in anxiety-like behavior and reward and is reported to express high levels of CB1R. We aimed to reveal the role of CB1R in BLA for ACPA-induced behavior. AM251, a CB1R selective antagonist, was administered intra-BLA before i.p. administration of ACPA. Intra-BLA administration of AM251 inhibited ACPA-induced anxiolytic-like behavior and place preference. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis.
全球吸食大麻的人数正在增加。然而，精神科效应和成瘾形成的机制仍不清楚。针对大麻成瘾的医学治疗方法尚未建立。大麻中的主要活性物质Δ9-四氢大麻酚（THC）与大脑中的大麻素 1 型受体（CB1R）结合并影响其功能。通过腹腔内（i.p.）给予 arachidonylcyclopropylamide（ACPA），一种 CB1R 选择性激动剂，然后进行了两项关于焦虑和成瘾的行为实验。ACPA 的给药导致高架十字迷宫测试中的焦虑样行为。此外，ACPA 增加了条件性位置偏爱（CPP）测试中的位置偏好。本研究的重点是基底外侧杏仁核（BLA），它与焦虑样行为和奖励有关，并且据报道表达高水平的 CB1R。我们旨在揭示 BLA 中的 CB1R 在 ACPA 诱导的行为中的作用。AM251 是一种 CB1R 选择性拮抗剂，在腹腔内给予 ACPA 之前在 BLA 内给药。BLA 内给予 AM251 抑制了 ACPA 诱导的焦虑样行为和位置偏好。这些结果表明，BLA 中的 CB1R 有助于由大麻的急性或慢性使用引起的行为障碍。
