Pedrazzi João F C, Silva-Amaral Danyelle, Issy Ana C, Gomes Felipe V, Crippa José A, Guimarães Francisco S, Del Bel Elaine
Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Pharmacol Biochem Behav. 2024 Dec;245:173879. doi: 10.1016/j.pbb.2024.173879. Epub 2024 Sep 19.
Individuals with schizophrenia (SCZ) often present sensorimotor gating impairments that can be investigated by the prepulse inhibition test (PPI). PPI disruption can be mimicked experimentally with psychostimulants such as amphetamine and attenuated/reversed by antipsychotics. Cannabidiol (CBD), the main non-psychotomimetic component of the Cannabis sativa plant, produces antipsychotic-like effects in clinical and preclinical studies. CBD can interact with many pharmacological targets, but the mechanisms involved in its antipsychotic activity are unclear. Using amphetamine-induced PPI disruption in mice, we investigated the involvement of four CBD potential pharmacological targets (CB1, CB2 TRPV1, and 5-HT1A receptors) in its antipsychotic properties. CBD effects were blocked by the TRPV1 antagonist capsazepine and, to a greater extent, by the 5-HT1A receptor antagonist WAY100635. No effect was observed with the CB1 (AM251) or CB2 (AM630) receptor antagonists. These results corroborate findings showing the antipsychotic effects of CBD in the PPI model and indicate that they involve the participation of TRPV1 and 5-HT1A receptors.
精神分裂症（SCZ）患者常表现出感觉运动门控障碍，可通过前脉冲抑制试验（PPI）进行研究。使用苯丙胺等精神兴奋剂可在实验中模拟PPI破坏，而抗精神病药物可减轻/逆转这种破坏。大麻二酚（CBD）是大麻植物的主要非致幻成分，在临床和临床前研究中具有类似抗精神病的作用。CBD可与多种药理学靶点相互作用，但其抗精神病活性所涉及的机制尚不清楚。利用苯丙胺诱导的小鼠PPI破坏，我们研究了CBD的四个潜在药理学靶点（CB1、CB2、TRPV1和5-HT1A受体）在其抗精神病特性中的作用。TRPV1拮抗剂辣椒素可阻断CBD的作用，5-HT1A受体拮抗剂WAY100635在更大程度上可阻断其作用。CB1（AM251）或CB2（AM630）受体拮抗剂未观察到任何作用。这些结果证实了在PPI模型中CBD具有抗精神病作用的研究发现，并表明其作用涉及TRPV1和5-HT1A受体的参与。
