Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice

Author(s)

Gomes, Felipe V. ^{[1, 2]} ; Del Bel, Elaine A. ^{[1, 3]} ; Guimaraes, Francisco S. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept Morphol Physiol & Stomatol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 46, p. 43-47, OCT 1 2013.
• Web of Science Citations: 27

Abstract

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans. It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson's patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders. To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms. The catalepsy test is largely used to investigate impairments of motor function caused by interference on striatal function. Male Swiss mice received acute pretreatment with CBD (5, 15, 30 or 60 mg/kg, ip) 30 min prior to the D-2 receptor antagonist haloperidol (0.6 mg/kg), the non-selective nitric oxide synthase (NOS) inhibitor L-nitro-N-arginine (L-NOARG, 80 mg/kg) or the CB1 receptor agonist WIN55,212-2 (5 mg/kg). The mice were tested 1, 2 or 4 h after haloperidol, L-NOARG or WIN55,212-2 injection. These drugs significantly increased catalepsy time and this effect was attenuated dose-dependently by CBD. CBD, by itself, did not induce catalepsy. In a second set of experiments the mechanism of CBD effects was investigated. Thirty minutes before CBD (30 mg/kg) the animals received the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg). The anticataleptic effect of CBD was prevented by WAY100635. These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D-2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 10/17343-0 - Evaluation of CBD effects on the molecular and behavioral changes induced by repeated treatment with MK-801
• Grantee: Felipe Villela Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate