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

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.

Long-term changes in social interaction and reward following repeated MDMA administration to adolescent rats without accompanying serotonergic neurotoxicity

“…In the current study, the first injection of MDMA produced the expected hyperlocomotion and components of the serotonin syndrome including flat body posture (Slikker et al 1989;Spanos and Yamamoto 1989;Marston et al 1999), consistent with an acute increase in synaptic levels of serotonin and dopamine (Shankaran and Gudelsky 1998;Iravani et al 2000). This was followed, at 45 min post-injection, by a significant, approximately 1°C, drop in core body temperature.…”

“…Although the precise underlying pharmacological mechanisms have not been established in humans, carrier-mediated release and/or inhibition of reuptake of 5-hydroxytryptamine (5-HT) and dopamine appear to account for the acute behavioural correlate seen with similar doses in rodents (Green et al 1995;Iravani et al 2000;Morgan 2000). In addition, MDMA reduces the activity of the biosynthetic enzyme tryptophan hydroxylase (Schmidt and Taylor 1987) and causes a longer-term depletion of the product, 5-HT, preferentially from fine-diameter neurones arising from the dorsal raphé nucleus (Mamounas et al 1991).…”

Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review

“…However, increases in synaptic dopamine and noradrenaline may also play a role. 6,7 Although it would be expected that a dose-response relationship would exist between serum MDMA levels and toxicity, this does not appear to be true. 8 Cases have been reported with serum levels as high as 7.72 mg/L with virtually no symptomatology and, conversely, fatalities have been reported with levels of 0.11 mg/L.…”

Genetic Deletion of Trace Amine 1 Receptors Reveals Their Role in Auto-Inhibiting the Actions of Ecstasy (MDMA)

“…Further, it prevents 5-HT reuptake (Iravani et al, 2000) and inhibits the activity of the catabolytic enzyme monoamine oxidase A (Leonardi and Azmitia, 1994). Concomitant elevations in dopamine (DA) and noradrenaline (NA) levels occur either via a similar pattern of direct actions upon catecholaminergic pathways (Gough et al, 2002;Baumann et al, 2005Baumann et al, , 2008 and/or events downstream of serotonergic transmission, such as activation of 5-HT 2A receptors (Gobert et al, 2000).…”