Original Article

Neuropsychopharmacology (2006) 31, 795–803. doi:10.1038/sj.npp.1300838; published online 27 July 2005

Preclinical Research

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Leonora E Long1, Daniel T Malone1 and David A Taylor1

1Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Victoria, Australia

Correspondence: LE Long, Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia. Tel: +61 3 9903 9085; Fax: +61 3 9903 9638; E-mail: leonora.long@vcp.monash.edu.au

Received 7 January 2005; Revised 23 May 2005; Accepted 7 June 2005; Published online 27 July 2005.

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Abstract

Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1) and also to inhibit the hydrolysis and cellular uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such as schizophrenia and may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3–1 mg/kg i.p.) dose dependently disrupted PPI while cannabidiol (1–15 mg/kg i.p.), when administered with vehicle, had no effect on PPI. Cannabidiol (5 mg/kg i.p.) successfully reversed disruptions in PPI induced by MK-801 (1 mg/kg i.p.), as did the atypical antipsychotic clozapine (4 mg/kg i.p.). Pretreatment with capsazepine (20 mg/kg i.p.) prevented the reversal of MK-801-induced disruption of PPI by cannabidiol, providing preliminary evidence that TRPV1 receptors are involved in the reversal of MK-801-induced sensorimotor gating deficits by cannabidiol.

Keywords:

cannabidiol, capsazepine, endocannabinoid, schizophrenia, sensorimotor gating, vanilloid receptor

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