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

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.

Role of the endocannabinoid system in a mouse model of Fragile X undergoing neuropathic pain

“…In addition, sham mice partially lacking CB2 showed an enhanced depressive‐like behaviour, suggesting an antidepressant function of CB2 under basal conditions. Accordingly, previous studies targeting CB2 with pharmacological tools or genetic deletion have also shown antidepressant effects of CB2 activation (Ishiguro et al., 2018; Liu et al., 2017). Moreover, sham mice partially lacking CB2 did not show cognitive deficits under basal conditions, as other studies have reported when this receptor was pharmacologically blocked (Busquets‐Garcia et al., 2013).…”

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

“…CB 2 receptors located on neurons and microglia in the spinal cord contribute to central sensitization in OA [ 98 ]. CB 2 receptors might play a role in the several neurological diseases, such as Alzheimer disease [ 99 , 100 ], depression [ 101 , 102 ], Parkinson disease [ 103 ] or memory formation [ 104 , 105 ]. However, since CB 2 in the other than peripheral location has been investigated recently, more studies are needed to clarify its role in various conditions.…”

Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders

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