Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice

Author(s)

Sonego, Andreza B. ^{[1, 2]} ; 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, Med Sch Ribeirao Preto, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept Morphol Physiol & Stomatol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 309, p. 22-28, AUG 1 2016.
• Web of Science Citations: 10

Abstract

Cannabidiol (CBD) is a major wnon-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60 mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6 mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1 mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30 min before haloperidol administration. Also, CBD, administered 2.5 h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60 nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. (C) 2016 Elsevier B.V. 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