Tumour necrosis factor alpha suppression by MDMA is mediated by peripheral heteromeric nicotinic receptors

Abstract

MDMA is an illegal drug widely used by young people. The present study aimed to determine the involvement of different nicotinic acetylcholine receptor (nAChR) subtypes in the suppressive effect of MDMA in TNF-α production. Dihydrobetaerythroidine (antagonist of heteromeric nAChR), and hexamethonium (antagonist of peripheral nAChR), fully antagonized the effect of MDMA. Conversely, methyllycaconitine (antagonist of homomeric nAChR), did not modify it. From in vitro experiments, a direct effect was ruled out. In this study we provide the first evidence that in rodents MDMA impairs the production of TNF-α by activation of heteromeric nAChR expressing beta-2 subunits located in the periphery.

Keywords::

• MDMA
• ecstasy
• TNF-α; nicotinic receptors
• rat
• mice

Acknowledgments

We are grateful to the Language Advisory Service of the University of Barcelona for revising the language of the manuscript. Thanks go also to M. Amat, J. Bosch and N. Llor from the Organic Chemistry Laboratory of the University of Barcelona for the spectral analysis of MDMA, demonstrating its chemical purity.

Declaration of interest: This study was supported by grants from the Drug of Abuse National Program (2008/003) and the Ministry of Science and Innovation (SAF2006-01456). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.