Actions of MDMA at glutamatergic neuromuscular junctions.
3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") compels mammalian serotonergic neurons to release serotonin (5-HT). In this study, MDMA altered synaptic transmission presynaptically by enhancing quantal release in two model glutamatergic synapses-the neuromuscular junction (NMJ) of the crayfish opener muscle, which is enhanced by exogenous 5-HT application, and the NMJ of a larval body wall muscle in Drosophila melanogaster, which is insensitive to exogenous 5-HT application. At the crayfish NMJ, MDMA mimicked the actions of 5-HT but only at a substantially higher concentration. At the Drosophila NMJ, MDMA altered synaptic transmission but not through a 5-HT receptor. Using simple invertebrate preparations, we have demonstrated an additional non-serotonergic mechanism of MDMA activity that has not yet been addressed in vertebrate systems and that may play an important role in understanding the mechanism of action for a commonly abused drug.
Sparks
G M
GM
Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA.
Dasari
S
S
Cooper
R L
RL
D000818:Animals; D003400:Astacoidea; D004331:Drosophila melanogaster; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism*; D006213:Hallucinogens / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D006213:Hallucinogens; D018698:Glutamic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine