3,4-Methylenedioxymethamphetamine (MDMA) Alters Synaptic Dopamine Release in the Dorsal Striatum Through Nicotinic Receptors and DAT Inhibition.
An increase of extracellular dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA). Although this drug has been reported to affect the DA uptake transporter (DAT), it might activate other mechanisms to regulate the outflow of DA in the brain. Our aim was to examine the overall effects of MDMA on the release of DA in the striatum. We studied the effect of MDMA on stimulus-evoked synaptic DA release in dorsal striatal slices of mice using in vitro amperometric techniques. We also tested the effects of MDMA on the nicotine-induced responses in substantia nigra pars compacta (SNpc) neurons using intracellular electrophysiological recordings. MDMA (1-30 µM) depressed the amplitude and prolonged the decay-time of synaptic DA release in the striatum. Interestingly, in the presence of the broad nicotinic receptor antagonist mecamylamine, and the more selective α