MDMA alters immunity to infections of the peripheral and central nervous systems

DESCRIPTION (provided by applicant): Teenagers and young adults are the age group most likely to abuse a growing list of compounds known as "club drugs". Ecstasy, or 3,4 methylenedioxymethamphetamine (MDMA), is currently one of the most popular club drugs of abuse, and we are just beginning to learn about the deleterious effects this drug can have on central nervous system function of these young adults. While we suspect there is a link between some diseases and club drug abuse, there have been no studies to investigate whether Ecstasy might have such a deleterious effect on immune function within the central nervous system or in the periphery during microbial diseases. This is somewhat surprising, since 3,4- methylenedioxymethamphetamine is one of the most commonly abused drugs by young adults. Furthermore, Ecstasy has its primary effects on the central nervous system and can induce the very social behaviors that would increase the likelihood of exposure to various diseases. The present proposal will use mouse models to investigate how 3,4-methylenedioxymethamphetamine can alter the protective host response to a viral infection. Specifically, this proposal will investigate the ability of 3,4-methylenedioxymethamphetamine to modulate the immune response of leukocytes following in vivo or in vitro exposure of this drug of abuse. Pharmacological studies will allow an understanding of the mechanims by which 3,4-methylenedioxymethamphetamine might exert its effects. Particular attention will be given to the importance of trace amine receptor-mediated mechanisms. In addition, the direct effects of 3,4-methylenedioxymethamphetamine and its metabolites on leukocyte function will be assessed using cultures of purified cells followed by an evaluation of cytokine and chemokine secretion and expression of cell surface molecules. Complementary studies will be performed on tissues from mice with a viral infection. These studies will define mechanisms by which the club drug, Ecstasy, can modulate inflammatory responses following infection, and represent the first effort to link the use of Ecstasy with exacerbated diseases of young adults.