Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Abstract

The party drug 3,4-methylenedioxymethamphetamine -better known as MDMA or ecstasy-has numerous effects on the human body, characterized by a rush of energy, euphoria and empathy. However, also a multitude of toxic/neurotoxic effects have been ascribed to MDMA, based upon case reports and studies in animals. Given the intrinsic difficulties associated with controlled studies in human beings, most of our insights into the biology of MDMA have been gained through animal studies. The vast majority of these studies utilizes a pharmacological approach to elucidate the mechanisms by which MDMA exerts its effects.Advances in genetics during the last decade have led to the development of several mouse models (transgenic or knockout) that have greatly contributed to our understanding of MDMA biology. This review provides an overview of these genetically modified animal models, in the light of some characteristic effects of MDMA, e.g. hyperlocomotion, neurotoxicity, hyperthermia, behaviour or rewarding. Without a shadow of a doubt, the next decade will bring many more advanced animal models, such as mice with site-specific deletion or rescue of genes and more genetically modified rat models. These models will further improve our knowledge on the pharmacology and toxicity of MDMA and, possibly, may assist in developing therapies coping with potential damage in abusers of MDMA and other drugs, as well as in patients suffering from specific neuronal pathologies.MDMA in advanced animal models 3

Looking for prosocial genes: ITRAQ analysis of proteins involved in MDMA-induced sociability in mice

“…In addition, the possibility to evaluate the sociability induced by MDMA in mice opens new possible research approaches by using the different lines of genetically modified mice now available. The mechanisms of MDMA action have been mainly investigated with selective agonists or antagonists of the potential receptors involved in its pharmacological responses, and more recently, using genetically modified mice (Stove et al, 2010). Multiple studies associate social fear and sociability with modulation of the inhibitory serotonergic 5-HT1A receptor (Akimova et al, 2009), and our findings on pharmacological blockade of this receptor on MDMA-induced sociability support this hypothesis.…”