Tumour necrosis factor alpha suppression by MDMA is mediated by peripheral heteromeric nicotinic receptors.
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-alpha 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-alpha by activation of heteromeric nAChR expressing beta-2 subunits located in the periphery.