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Abstract Title:

β-Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents.

Abstract Source:

Br J Pharmacol. 2020 May ;177(9):2058-2072. Epub 2020 Feb 15. PMID: 31883107

Abstract Author(s):

Yi He, Ewa Galaj, Guo-Hua Bi, Xiao-Fei Wang, Eliot Gardner, Zheng-Xiong Xi

Article Affiliation:

Yi He

Abstract:

BACKGROUND AND PURPOSE: β-Caryophyllene (BCP) is a plant-derived terpenoid used as a food additive for many decades. Recent studies indicate that BCP is a cannabinoid CBreceptor agonist with medical benefits for a number of human diseases. However, little is known about its therapeutic potential for drug abuse and addiction.

EXPERIMENT APPROACH: We used pharmacological, transgenic, and optogenetic approaches to systematically evaluate the effects of BCP on nicotine-taking and nicotine-seeking behaviour 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 CBreceptor antagonist, but not by AM251, a selective CBreceptor antagonist, suggesting involvement of a CBreceptor mechanism. Genetic deletion of CBreceptors in mice blocked the reduction in nicotine self-administration produced only by low doses, but not by high doses, of BCP, suggesting involvement of both CBand non-CBreceptor mechanisms. Furthermore, in the intracranial self-stimulation paradigm, BCP attenuated electrical brain-stimulation reward and nicotine-enhanced brain-stimulation reward in rats. Lastly, BCP also attenuated brain-stimulation reward maintained by optogenetic stimulation of dopaminergic neurons in the ventral tegmental area in DAT-cre mice, suggesting the involvement of a dopamine-dependent mechanism in BCP's action.

CONCLUSIONS AND IMPLICATIONS: The present findings suggest that BCP has significant anti-nicotine effects via both CBand non-CBreceptor mechanisms and, therefore, deserves further study as a potential new pharmacotherapy for cigarette smoking cessation.

Study Type : Animal Study

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