Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans

NEUROPHARMACOLOGY

卷:135

Article

Skosnik, Patrick D.¹  Hajos, Mihaly²  Cortes-Briones, Jose A.¹  Edwards, Chad R.³  Pittman, Brian P.¹  Hoffmann, William E.²  Sewell, Andrew R.¹  D'Souza, Deepak C.¹  Ranganathan, Mohini¹ 

[1] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Comparat Med, 333 Cedar St, New Haven, CT 06510 USA

[3] Dev Neuropsychol Serv PC, South Bend, IN 46615 USA

关键词: Cannabinoid;    Neural oscillations;    Theta;    EEG;    P50;    Sensory gating;   

DOI  :  10.1016/j.neuropharm.2018.03.036

来源: Elsevier

【 摘 要 】

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 electroen-cephalography (EEG) and local field potentials (LFPs), respectively. Human subjects (n = 15) completed four test days during which they received intravenous delta-9-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), Delta(9)-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 Delta(9)-THC (p < 0.007) and Delta(9)-THC + CBD (p < 0.004) disrupted P50 gating ratio compared to placebo, while CBD alone had no effect. Delta(9)-THC (p <0.048) and Delta(9)-THC + CBD (p < 0.035) decreased S1 evoked theta power, and in the Delta(9)-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 Si, 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. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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