Direct effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices
Mahmoud M. Iravani, Daniel Asari, Jyoti C. Patel, Walter J. Wieczorek, Zygmunt L. Kruk
Synapse April 27, 2000 DOI: 10.1002/(sici)1098-2396(20000615)36:4<275::aid-syn4>3.0.co;2-# via OpenAlex
Summary
AI-generated from the abstractMDMA does not directly cause the release of serotonin or dopamine in brain slices from rats, contrary to some earlier assumptions. Instead, it acts as a potent inhibitor of the reuptake of both neurotransmitters, slowing their removal from the synapse. MDMA also potentiated electrically stimulated serotonin release in the substantia nigra pars reticulata and dopamine release in the caudate putamen, but had no effect on stimulated release in the dorsal raphé nucleus or nucleus accumbens. These findings clarify MDMA's mechanism of action as distinct from that of amphetamine.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat brain slices |
| Intervention | pressure ejection of MDMA |
| Topics | Serotonin |
| Keywords | Nucleus accumbens Dopamine Caudate nucleus Putamen Dorsal raphe nucleus |
| Citations | 56 |
| Key finding | MDMA is not a releaser of dopamine or serotonin but is a potent inhibitor of their uptake, and it potentiates electrically stimulated serotonin release in the substantia nigra pars reticulata and dopamine release in the caudate putamen. |
Abstract
We examined the effects of pressure ejected 3, 4-methylenedioxymethamphetamine (MDMA) from a micropipette on direct chemically stimulated release, and on electrically stimulated serotonin (5-HT) or dopamine (DA) release in the caudate putamen (CPu), nucleus accumbens (NAc), substantia nigra pars reticulata (SNr), and the dorsal raphé nucleus (DRN) brain slices of rat, using fast cyclic voltammetry (FCV). MDMA is electroactive, oxidising at +1100 mV. When the anodic input waveform was reduced from +1.4 to +1.0 volt, MDMA was not electroactive. Using this waveform, pressure ejection of MDMA did not release 5-HT or DA in brain slices prepared from any of the nuclei studied. MDMA significantly potentiated electrically stimulated 5-HT release in the SNr and DA release in CPu. In the DRN or in the NAc, MDMA was without effect on peak electrically stimulated 5-HT or DA release. The rates of neurotransmitter uptake, expressed as t(1/2), were in all cases significantly decreased after MDMA. The results indicate that MDMA, unlike (+)amphetamine, is not as a releaser of DA or 5-HT, it is a potent inhibitor of both DA and 5-HT uptake.