Nouri Kiana, Anooshe Mahsa, Karimi-Haghighi Saeideh, Mousavi Zahra, Haghparast Abbas
Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Neurochem Res. 2021 Aug;46(8):2008-2018. doi: 10.1007/s11064-021-03350-w. Epub 2021 May 15.
Cannabidiol (CBD) is a non-psychotomimetic compound with strong potential to decrease the psychostimulant's rewarding effect with unclear receptors. Furthermore, as a part of the reward circuit, the hippocampus plays a crucial role in regulating the reward properties of drugs as determined by conditioned place preference (CPP). In the current research, CPP was used to evaluate the role of intra-CA1 microinjection of D1-like dopamine receptor antagonists in CBD's inhibitory effect on the acquisition and expression phases of methamphetamine (METH). Animals were treated by METH (1 mg/kg; sc) in a five-day schedule to induce CPP. To find out the impact of D1-like dopamine receptor antagonist, SCH23390, in the CA1 on the inhibitory influence of CBD on the acquisition of METH, the rats received intra-CA1 administration of SCH23390 (0.25, 1, and 4 µg/0.5 µl) following ICV treatment of CBD (10 µg/5 µl) over conditioning phase of METH. Furthermore, animals were given SCH23390 in the CA1 ensuing ICV microinjection of CBD (50 µg/5 µl) in the expression phase of METH to rule out the influence of SCH23390 on the suppressive effect of CBD on the expression of METH CPP. Intra-CA1 microinjection of SCH23390 abolished CBD's suppressive impact on both METH-induced CPP phases without any side effect on the locomotion. The current research disclosed that CBD inhibited the rewarding characteristic of METH via D1-like dopamine receptors in the CA1 region of the hippocampus.
大麻二酚（CBD）是一种无致幻作用的化合物，具有显著降低精神兴奋剂奖赏效应的潜力，但其作用受体尚不明确。此外，海马体作为奖赏回路的一部分，在通过条件性位置偏爱（CPP）测定的药物奖赏特性调节中起着关键作用。在本研究中，采用CPP来评估在CA1区域微量注射D1样多巴胺受体拮抗剂对CBD抑制甲基苯丙胺（METH）获得和表达阶段作用的影响。动物按五天的给药计划接受METH（1 mg/kg；皮下注射）以诱导CPP。为了探究CA1区域的D1样多巴胺受体拮抗剂SCH23390对CBD抑制METH获得的影响，在METH条件化阶段经脑室内（ICV）给予CBD（10 µg/5 µl）后，大鼠接受CA1区域内SCH23390（0.25、1和4 µg/0.5 µl）给药。此外，在METH表达阶段经ICV微量注射CBD（50 µg/5 µl）后，给予动物CA1区域内的SCH23390，以排除SCH23390对CBD抑制METH CPP表达作用的影响。CA1区域内微量注射SCH23390消除了CBD对METH诱导的CPP两个阶段的抑制作用，且对运动无任何副作用。本研究表明，CBD通过海马体CA1区域的D1样多巴胺受体抑制METH的奖赏特性。
