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Table of Contents
Vol. 54, No. 4, 2006
Issue release date: April 2007
Section title: Original Paper
Editor's Choice -- Free Access
Neuropsychobiology 2006;54:231–246

Neuropsychobiological Evidence for the Functional Presence and Expression of Cannabinoid CB2 Receptors in the Brain

Onaivi E.S.
Department of Biology, William Paterson University, Wayne, N.J., USA
email Corresponding Author

Emmanuel S. Onaivi, PhD

Department of Biology

William Paterson University

Wayne, NJ 07470 (USA)

Tel. +1 973 720 3453, Fax +1 973 720 2338, E-Mail Onaivie@wpunj.edu

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For over a decade, until recently, it was thought that marijuana acts by activating brain-type cannabinoid receptors called CB1, and that a second type called CB2 cannabinoid receptor was found only in peripheral tissues. Neuronal CB2 receptors in the brain had been controversial. We reported the discovery and functional presence of CB2 cannabinoid receptors in the mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays were used to determine the functional expression of CB2 cannabinoid receptors in the rat brain and mouse brain exposed to chronic mild stress or treated with abused drugs. RT-PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in the brain. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system. In humans, there was a high incidence of Q63R polymorphism in the CB2 gene in Japanese alcoholics and depressed subjects. Contrary to the prevailing view that CB2 cannabinoid receptors are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 cannabinoid receptors and their gene transcripts are widely distributed in the brain. This multifocal expression of iCB2 in the brain suggests that CB2 receptors may play broader roles than previously anticipated and may therefore be exploited as new targets in the treatment of depression and substance abuse.

© 2006 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: January 02, 2006
Accepted: December 17, 2006
Published online: April 04, 2007
Issue release date: April 2007

Number of Print Pages: 16
Number of Figures: 7
Number of Tables: 0

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

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