Synthetic cannabinoids enhanced ethanol-induced motor impairments through reduction of central glutamate neurotransmission
Synthetic cannabinoids enhanced ethanol-induced motor impairments through reduction of central glutamate neurotransmission
复制标题
DOI：
10.1016/j.taap.2020.115283
复制
发表时间：
2020-12-01
影响因子：
3.8
通讯作者：
Tomiyama, Ken-ich
中科院分区：
文献类型：
--
作者：
Funada, Masahiko;Takebayashi-Ohsawa, Mika;Tomiyama, Ken-ich
大麻或合成大麻素和酒精经常一起使用，这些组合会导致运动障碍，从而导致机动车事故。这项研究除了检查小脑的神经化学变化外，还研究了合成大麻素和乙醇的联合使用及其对小鼠运动协调的影响。乙醇（2 g/kg，腹腔注射）在小鼠加速转棒试验中显着诱导运动损伤。此外，当与合成大麻素 JWH-018 或 AB-CHMINACA 结合使用时，乙醇引起的运动障碍进一步加剧。合成大麻素的增强作用被选择性CB1受体拮抗剂AM251预处理完全拮抗，但不被选择性CB2受体拮抗剂AM630预处理。神经化学研究结果表明，在乙醇引起的运动障碍期间，乙醇会导致小脑细胞外谷氨酸水平降低。乙醇与 JWH-018 联合使用时，除了会增强运动障碍之外，这些组合还可以增强小脑细胞外谷氨酸水平的降低。我们还使用微电极阵列记录来检查乙醇和/或 JWH-018 对小鼠小脑原代培养物中自发网络活动的影响。结果表明，乙醇与 JWH-018 联合显着降低了原代小脑培养物中的自发神经元网络活动。我们的研究结果表明，合成大麻素会增强乙醇引起的运动障碍，这些效应可能由 CB1 受体介导。小脑神经传递的急剧减少可能在乙醇与合成大麻素联合引起的运动障碍中发挥重要作用。
Marijuana or synthetic cannabinoids and alcohol are often used together, with these combinations causing motor impairments that can subsequently lead to motor vehicle accidents. This study investigated the combined use of both synthetic cannabinoids and ethanol and their effect on motor coordination in mice in addition to examining the neurochemical changes in the cerebellum. Ethanol (2 g/kg, i.p.) significantly induced motor impairment in the accelerating rotarod test in mice. Furthermore, ethanol-induced motor impairments were further accentuated when combined with the synthetic cannabinoid, JWH-018 or AB-CHMINACA. The enhancement effects of the synthetic cannabinoids were completely antagonized by pretreatment with the selective CB1 receptor antagonist AM251, but not by the selective CB2 receptor antagonist AM630. Neurochemical study results showed that ethanol caused a reduction in the extracellular glutamate levels in the cerebellum during periods of ethanol-induced motor impairment. In addition to the enhanced motor impairment seen when ethanol was combined with JWH-018, these combinations also enhanced the reduction of the extracellular glutamate levels in the cerebellum. We additionally used microelectrode array recordings to examine the effects of ethanol and/or JWH-018 on the spontaneous network activity in primary cultures from mouse cerebellum. Results showed that ethanol combined with JWH-018 significantly reduced spontaneous neuronal network activity in the primary cerebellar culture. Our findings demonstrate that ethanol-induced motor impairments are enhanced by synthetic cannabinoids, with these effects potentially mediated by CB1 receptors. An accentuated reduction of neurotransmissions in the cerebellum may play an important role in motor impairments caused by ethanol combined with synthetic cannabinoids.