Hassanlou Amir Arash, Jamali Shole, RayatSanati Kimia, Mousavi Zahra, Haghparast Abbas
Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Brain Res Bull. 2021 Jul;172:43-51. doi: 10.1016/j.brainresbull.2021.04.007. Epub 2021 Apr 16.
The main problem with addiction is a relapse with a high rate in methamphetamine (METH) abusers. Using addictive drugs repetitively will cause the reward. METH reward is due to an increase in dopamine levels, and the endocannabinoid system (ECS) has a modulatory role in reward through CB1 receptors. On the other hand, the hippocampus plays an important role in learning and memory, so it is involved in the neuroplasticity caused by METH abuse. Cannabidiol (CBD) has been shown to reduce the effects of METH through different mechanisms such as increasing the ECS activity, regulating emotional memory in the ventral hippocampus through D2-like dopamine receptors, and decreasing the mesolimbic dopaminergic activity. The present study tried to find out the role of hippocampal CA1 D2-like dopamine receptors (D2R) in the effects of cannabidiol on the acquisition and expression of METH-induced conditioned place preference (METH-CPP) in rats by using microinjection of sulpiride as a D2R antagonist. For this purpose, different groups of animals received different doses of sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO; CA1), once prior to the injection of CBD (10 μg/5 μL for acquisition and 50 μg/5 μL for expression; ICV) and once in the absence of CBD. Control groups were also considered. In brief, findings showed that cannabidiol decreases METH-induced CPP. Intra-CA1 administration of sulpiride reversed the decreasing effects of cannabidiol on METH-induced CPP in both acquisition and expression phases but more prominent in the expression phase. The results showed that sulpiride did not affect the METH-induced CPP in the absence of cannabidiol. In conclusion, this study demonstrated that cannabidiol decreased METH-induced CPP in part through interaction with hippocampal CA1 D2-dopamine receptors.
成瘾的主要问题在于甲基苯丙胺（METH）滥用者的复发率很高。反复使用成瘾性药物会产生奖赏效应。METH奖赏效应是由于多巴胺水平升高所致，而内源性大麻素系统（ECS）通过CB1受体在奖赏过程中发挥调节作用。另一方面，海马体在学习和记忆中起重要作用，因此它参与了METH滥用引起的神经可塑性变化。大麻二酚（CBD）已被证明可通过多种不同机制减轻METH的作用，例如增加ECS活性、通过D2样多巴胺受体调节腹侧海马体中的情绪记忆以及降低中脑边缘多巴胺能活性。本研究试图通过微量注射舒必利（一种D2R拮抗剂）来探究海马CA1区D2样多巴胺受体（D2R）在大麻二酚对大鼠METH诱导的条件性位置偏爱（METH-CPP）的获得和表达的影响中所起的作用。为此，不同组的动物在注射CBD（获取阶段为10μg/5μL，表达阶段为50μg/5μL；脑室内注射）之前一次以及在不注射CBD时一次接受不同剂量的舒必利（0.25、1和4μg/0.5μL二甲基亚砜；CA1区注射）。同时也设立了对照组。简而言之，研究结果表明大麻二酚可降低METH诱导的CPP。在CA1区内注射舒必利可逆转大麻二酚在获取和表达阶段对METH诱导的CPP的降低作用，但在表达阶段更为显著。结果表明，在没有大麻二酚的情况下，舒必利不会影响METH诱导的CPP。总之，本研究表明大麻二酚部分通过与海马CA1区D2-多巴胺受体相互作用来降低METH诱导的CPP。
