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Molecules 2018, 23(8), 1836; https://doi.org/10.3390/molecules23081836

Cannabinoid CB2 Receptor Gene and Environmental Interaction in the Development of Psychiatric Disorders

1
Department of Neuropsychiatry and Clinical Ethics, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan
2
Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
3
National Institute on Aging-IRP, NIH, Baltimore, MD 21224, USA
4
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
5
Department of Biology, William Paterson University, Wayne, NJ 07470, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Mauro Maccarrone
Received: 24 May 2018 / Revised: 18 July 2018 / Accepted: 20 July 2018 / Published: 24 July 2018
(This article belongs to the Special Issue Emerging Topics in (Endo)Cannabinoid Signalling)
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Abstract

CB2 cannabinoid receptor (CB2R) gene is associated with depression. We investigated the gene-environment interaction between CB2R function and diverse stressors. First, anxiety-like behavior during chronic-mild-stress (CMS) was evaluated in C57BL/6JJmsSlc mice following treatment with CB2R agonist JWH015 or inverse-agonist AM630. Second, locomotor activity and anxiety-like behavior were measured following exposure to an immune poly I:C stressor. Gene expressions of HPA axis related molecules, Fkbp5, Nr3c1 and Crf and pro-inflammatory cytokine Il-1b, as well as Bdnf as a key neurotrophin that supports neuron health, function, and synaptic plasticity, were determined in hippocampus of Cnr2 knockout mice, as indicators of stressful environment. CMS-induced anxiety-like behavior was enhanced by AM630 and reduced by JWH015 and fluvoxamine. Poly I:C reduced locomotor activity and increased anxiety-like behavior, and these effects were pronounced in the heterozygote than in the wild type mice. Fkbp5 and Nr3c1 expression were lower in the Cnr2 heterozygotes than in the wild type mice with Poly I:C treatment. These findings indicate that interaction between CB2R gene and stressors increases the risk of depression-like behaviors that may be linked with neuro-immune crosstalk. Further studies in human subjects are necessary to determine the role of CB2R and environmental interaction in the development of depression. View Full-Text
Keywords: endocannabinoid; cannabinoid CB2 receptor; Cnr2; depression; anxiety; chronic mild stress; neuro-immune signaling; HPA axis endocannabinoid; cannabinoid CB2 receptor; Cnr2; depression; anxiety; chronic mild stress; neuro-immune signaling; HPA axis
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Ishiguro, H.; Horiuchi, Y.; Tabata, K.; Liu, Q.-R.; Arinami, T.; Onaivi, E.S. Cannabinoid CB2 Receptor Gene and Environmental Interaction in the Development of Psychiatric Disorders. Molecules 2018, 23, 1836.

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