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Cannabidiol attenuates prepulse inhibition disruption by facilitating TRPV1 and 5-HT1A receptor-mediated
João F C Pedrazzi1, Danyelle Silva-Amaral2, Ana C Issy3
1Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Abstract:
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.
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