Role of CB2 cannabinoid receptors in the ameliorative effects of curcumin on BCG-induced depression in mice: Insights into peripheral inflammation and central NF-κB signaling

Abstract

Elevated peripheral inflammatory markers are associated with the development of several neurological disorders. Curcumin, a strong natural anti-inflammatory agent, has recently been identified as a potent agonist of the CB2 cannabinoid receptor. Since the function of CB2 receptors in neuropsychiatric illnesses is gaining increasing attention, the present study aimed to elucidate their involvement in the effects of curcumin on depressive phenotypes. The mice were inoculated with BCG and allowed 7 days to induce depression-like behavior. The animals were then administered curcumin alone or concomitantly with CB2 receptor agonist JWH133 or antagonist AM630, daily for 7 days, and subjected to the sucrose preference test, open field test, tail suspension test, and splash test. Further, the blood samples were analyzed for the TNF-α and IL-6 contents, and the brains were processed to estimate NF-κB and serotonin levels using the ELISA and HPLC techniques. The results showed a significant reversal of depressive episodes by curcumin in BCG-inoculated mice. The elevated plasma levels of TNF-α and IL-6 in depressed animals were associated with higher NF-κB and lower serotonin contents in the brain. The concentrations of these biochemical parameters were restored by curcumin treatment. Moreover, pre-treatment with JWH133 potentiated the effects of curcumin on behavioral and biochemical parameters, whereas AM630 attenuated the same. We suggest that curcumin, through its interaction with the CB2 receptor, may inhibit BCG-evoked activation of peripheral TNF-α and IL-6, which could prevent the stimulation of NF-κB in the brain, potentially leading to increased serotonin contents and alleviation of depressive phenotypes.