Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.
Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.
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大麻素受体介导的感觉门控和神经振荡破坏：大鼠和人类的转化研究。
DOI：
10.1016/j.neuropharm.2018.03.036
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发表时间：
2018
影响因子：
4.7
通讯作者：
Ranganathan,Mohini
中科院分区：
文献类型：
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作者：
Skosnik,PatrickD;Hajós,Mihály;Cortes-Briones,JoseA;Edwards,ChadR;Pittman,BrianP;Hoffmann,WilliamE;Sewell,AndrewR;D'Souza,DeepakC;Ranganathan,Mohini
大麻的使用与感觉门控和神经振荡的改变有关。然而，目前还不清楚大麻中的哪种成分是造成这些效应的原因，或者这些效应是否是大麻素受体1（CB 1 R）介导的。因此，本研究在人类和大鼠中分别利用脑电图（EEG）和局部场电位（LFP）检查大麻素给药是否会破坏感觉门控和诱发振荡。人类受试者（n = 15）完成了四个测试日，在此期间，他们接受静脉注射δ-9-四氢大麻酚（Δ9-THC），大麻二酚（CBD），Δ9-THC + CBD或安慰剂。受试者参与双击范例，结果测量包括P50门控比（S2/S1）和S1和S2的诱发功率。为了检查CB 1 R特异性，使用相同的范例向大鼠（n = 6）施用CB 1 R激动剂CP-55940、CP-55940+AM-251（CB 1 R拮抗剂）或媒介物。从CA 3和内嗅皮层记录LFP。与安慰剂相比，Δ9-THC（p < 0.007）和Δ9-THC + CBD（p < 0.004）都破坏了P50门控比，而CBD单独没有影响。Δ9-THC（p < 0.048）和Δ9-THC + CBD（p < 0.035）降低了S1诱发的θ功率，在Δ9-THC条件下，S1 θ与门控比率呈负相关（r =-0.629，p < 0.012（p < 0.048调整））。在大鼠中，CP-55940破坏了两个脑区的门控（p < 0.0001），AM-251逆转了这一点。此外，CP-55940降低了诱发的θ（p < 0.0077）和γ（p < 0.011）功率至S1，这被AM-251部分阻断。这些收敛的人类/动物数据表明，CB 1 R激动剂通过改变θ-带中的神经振荡来破坏感觉门控。此外，这表明内源性大麻素系统介导与感知和认知相关的θ振荡。
Cannabis use has been associated with altered sensory gating and neural oscillations. However, it is unclear which constituent in cannabis is responsible for these effects, or whether these are cannabinoid receptor 1 (CB1R) mediated. Therefore, the present study in humans and rats examined whether cannabinoid administration would disrupt sensory gating and evoked oscillations utilizing electroencephalography (EEG) and local field potentials (LFPs), respectively. Human subjects (n = 15) completed four test days during which they received intravenous delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), Δ9-THC + CBD, or placebo. Subjects engaged in a dual-click paradigm, and outcome measures included P50 gating ratio (S2/S1) and evoked power to S1 and S2. In order to examine CB1R specificity, rats (n = 6) were administered the CB1R agonist CP-55940, CP-55940+AM-251 (a CB1R antagonist), or vehicle using the same paradigm. LFPs were recorded from CA3 and entorhinal cortex. Both Δ9-THC (p < 0.007) and Δ9-THC + CBD (p < 0.004) disrupted P50 gating ratio compared to placebo, while CBD alone had no effect. Δ9-THC (p < 0.048) and Δ9-THC + CBD (p < 0.035) decreased S1 evoked theta power, and in the Δ9-THC condition, S1 theta negatively correlated with gating ratios (r = −0.629, p < 0.012 (p < 0.048 adjusted)). In rats, CP-55940 disrupted gating in both brain regions (p < 0.0001), and this was reversed by AM-251. Further, CP-55940 decreased evoked theta (p < 0.0077) and gamma (p < 0.011) power to S1, which was partially blocked by AM-251. These convergent human/animal data suggest that CB1R agonists disrupt sensory gating by altering neural oscillations in the theta-band. Moreover, this suggests that the endocannabinoid system mediates theta oscillations relevant to perception and cognition.