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Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain.
Ann N Y Acad Sci. 2006 Aug; 1074:514-36.AN

Abstract

Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in 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. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those 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 brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. 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 (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse.

Authors+Show Affiliations

Department of Biology, William Paterson University, Wayne, NJ 07470, USA. Onaivie@wpunj.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17105950

Citation

Onaivi, Emmanuel S., et al. "Discovery of the Presence and Functional Expression of Cannabinoid CB2 Receptors in Brain." Annals of the New York Academy of Sciences, vol. 1074, 2006, pp. 514-36.
Onaivi ES, Ishiguro H, Gong JP, et al. Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci. 2006;1074:514-36.
Onaivi, E. S., Ishiguro, H., Gong, J. P., Patel, S., Perchuk, A., Meozzi, P. A., Myers, L., Mora, Z., Tagliaferro, P., Gardner, E., Brusco, A., Akinshola, B. E., Liu, Q. R., Hope, B., Iwasaki, S., Arinami, T., Teasenfitz, L., & Uhl, G. R. (2006). Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Annals of the New York Academy of Sciences, 1074, 514-36.
Onaivi ES, et al. Discovery of the Presence and Functional Expression of Cannabinoid CB2 Receptors in Brain. Ann N Y Acad Sci. 2006;1074:514-36. PubMed PMID: 17105950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. AU - Onaivi,Emmanuel S, AU - Ishiguro,Hiroki, AU - Gong,Jian-Ping, AU - Patel,Sejal, AU - Perchuk,Alex, AU - Meozzi,Paul A, AU - Myers,Lester, AU - Mora,Zoila, AU - Tagliaferro,Patricia, AU - Gardner,Eileen, AU - Brusco,Alicia, AU - Akinshola,Babatunde E, AU - Liu,Qing-Rong, AU - Hope,Bruce, AU - Iwasaki,Shinya, AU - Arinami,Tadao, AU - Teasenfitz,Lindsey, AU - Uhl,George R, PY - 2006/11/16/pubmed PY - 2007/1/11/medline PY - 2006/11/16/entrez SP - 514 EP - 36 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1074 N2 - Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in 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. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those 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 brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. 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 (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/17105950/Discovery_of_the_presence_and_functional_expression_of_cannabinoid_CB2_receptors_in_brain_ L2 - https://doi.org/10.1196/annals.1369.052 DB - PRIME DP - Unbound Medicine ER -