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Abstract
BACKGROUND AND PURPOSE:
Beta-caryophyllene (BCP) is a dietary plant-derived terpenoid that has been used as a food additive for many decades. Recent studies indicate that BCP is a cannabinoid CB2 receptor (CB2R) agonist with medical benefits for a number of human diseases. However, little is known about its therapeutic potential for drug abuse and addiction.
EXPERIMENTAL APPROACH:
We used pharmacological, transgenic, and optogenetic approaches to systematically evaluate the effects of BCP on nicotine-taking and nicotine-seeking behavior in animal models of drug self-administration, electrical and optical brain-stimulation reward.
KEY RESULTS:
Systemic administration of BCP dose-dependently inhibited nicotine self-administration and motivation for nicotine seeking in rats and mice. The reduction in nicotine self-administration was blocked by AM630, a selective CB2R antagonist, but not by AM251, a selective CB1R antagonist, suggesting the involvement of a CB2R mechanism. Genetic deletion of CB2Rs in CB2-knockout mice blocked the reduction in nicotine self-administration produced only by low doses, but not high doses, of BCP, suggesting the involvement of both CB2 and non-CB2 receptor mechanisms. Furthermore, in the intracranial self-stimulation paradigm, BCP attenuated electrical brain-stimulation reward (BSR) and nicotine-enhanced BSR in rats. Lastly, BCP also attenuated BSR maintained by optogenetic stimulation of dopamine (DA) neurons in the ventral tegmental area in DAT-cre mice, suggesting the involvement of a DA-dependent mechanism in BCP’s action.
CONCLUSIONS AND IMPLICATIONS:
The present findings suggest that BCP has significant anti-nicotine effects via both CB2 and non-CB2 receptor mechanisms, and therefore, deserves further study as a potential new pharmacotherapy for cigarette smoking cessation.
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