Progress in brain cannabinoid CB2 receptor research: From genes to behavior

• Published in: Neuroscience and biobehavioral reviews Vol. 98; pp. 208 - 220
• Main Authors: Jordan, Chloe J., Xi, Zheng-Xiong
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.03.2019
• Subjects: Brain CB2 receptors; Cannabinoids; deltaΔ9-THC9; Neuronal CB2 receptors; VTA dopamine neurons; Brain CB2 receptors; Cannabinoids; deltaΔ9-THC9; VTA dopamine neurons; Neuronal CB2 receptors
• ISSN: 0149-7634; 1873-7528; 1873-7528
• DOI: 10.1016/j.neubiorev.2018.12.026

•Cannabinoid CB2R was initially assumed to be exclusively in the periphery.•Technological innovations have revealed functional CB2R expression in neurons.•Species differences exist in CB2R genes, receptor expression, and function.•Region-specific CB2R transcripts are found in the brain and periphery.•Brain CB2Rs are functional and neuroprotective against various insults. The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB2A is the major transcript isoform, while CB2A and CB2B transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.