Mirmohammadi Mahboobeh, Eskandari Kiarash, Koruji Morteza, Shabani Ronak, Ahadi Reza, Haghparast Abbas
Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cannabis Cannabinoid Res. 2024 Feb;9(1):89-110. doi: 10.1089/can.2022.0017. Epub 2022 Sep 1.
Methamphetamine (METH) is an addictive psychostimulant that facilitates dopamine transmission to the nucleus accumbens (NAc), resulting in alterations in the mesocorticolimbic brain regions. Cannabidiol (CBD) is considered the second most abundant component of cannabis and is believed to decrease the METH effects. Reversing psychostimulant-induced abnormalities in the mesolimbic dopamine system is the main mechanism for this effect. Various other mechanisms have been proposed: increasing endocannabinoid system activity and modulating gamma-aminobutyric acid (GABA) and glutamate neurons in NAc. However, the exact CBD action mechanisms in reducing drug addiction and relapse vulnerability remain unclear. The present study aimed to investigate the effects of intracerebroventricular (ICV) administrating 5, 10, and 50 μg/5 μL CBD solutions on the extinction period and reinstatement phase of a METH-induced conditioned place preference. This research also aimed to examine the NAc D1-like dopamine receptor (D1R) and D2-like dopamine receptor (D2R) roles in the effects of CBD on these phases, as mentioned earlier, using SCH23390 and sulpiride microinjections as an antagonist of D1R and D2R. The obtained results showed that microinjection of CBD (10 and 50 μg/5 μL, ICV) suppressed the METH-induced reinstatement and significantly decreased mean extinction latency in treated groups compared to both vehicles and/or untreated control groups. In addition, the results demonstrated that administrating intra-accumbal SCH23390 (1 and 4 μg/0.5 μL saline) reversed the inhibitory effects of CBD on extinction and reinstatement phases while different doses of sulpiride (0.25, 1, and 4 μg/0.5 μL; dimethyl sulfoxide 12%) could not alter the CBD effects. In summary, this study showed that CBD made shorter extinction latencies and suppressed the METH reinstatement, in part, by interacting with D1R but not D2R in the NAc.
甲基苯丙胺（METH）是一种成瘾性精神兴奋剂，它促进多巴胺向伏隔核（NAc）传递，导致中脑皮质边缘脑区发生改变。大麻二酚（CBD）被认为是大麻中含量第二丰富的成分，据信它能减轻METH的作用。逆转精神兴奋剂引起的中脑边缘多巴胺系统异常是这种作用的主要机制。还提出了各种其他机制：增加内源性大麻素系统活性以及调节NAc中的γ-氨基丁酸（GABA）和谷氨酸能神经元。然而，CBD在减少药物成瘾和复发易感性方面的确切作用机制仍不清楚。本研究旨在探讨脑室内（ICV）注射5、10和50μg/5μL CBD溶液对METH诱导的条件性位置偏爱消退期和复燃期的影响。本研究还旨在如前所述，使用SCH23390和舒必利微量注射作为D1R和D2R的拮抗剂，研究NAc D1样多巴胺受体（D1R）和D2样多巴胺受体（D2R）在CBD对这些阶段影响中的作用。获得的结果表明，与溶剂对照组和/或未治疗的对照组相比，脑室内注射CBD（10和50μg/5μL）抑制了METH诱导的复燃，并显著缩短了治疗组的平均消退潜伏期。此外，结果表明，伏隔核内注射SCH23390（1和4μg/0.5μL生理盐水）可逆转CBD对消退期和复燃期的抑制作用，而不同剂量的舒必利（0.25、1和4μg/0.5μL；二甲基亚砜12%）不能改变CBD的作用。总之，本研究表明，CBD通过与NAc中的D1R而非D2R相互作用，使消退潜伏期缩短并抑制了METH复燃。
