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Blockade of Striatal 5‐Hydroxytryptmine2Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine

Christopher J. Schmidt, C. K. Sullivan, G. M. Fedayal

Journal of Neurochemistry April 1, 1994 DOI: 10.1046/j.1471-4159.1994.62041382.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental animal study Peer reviewed
Population Awake, freely moving rats (in vivo microdialysis) and rat striatal slices (in vitro)
Interventions MDL 100 907 amperozide MDMA tetrodotoxin
Topics MDMA
Citations 130
Key findings The authors conclude that 5-HT2 receptors located in the striatum augment dopamine release produced by high doses of MDMA, and that these receptors appear to sit on nondopaminergic elements of the striatum. Intrastriatal MDL 100,907 inhibited MDMA-induced dopamine release in a concentration-dependent manner, while midbrain infusion had no effect and neither antagonist altered basal efflux or slice dopamine release.

Abstract

5-Hydroxytryptamine2 (5-HT2) receptor antagonists have been shown to interfere with the stimulation of striatal dopamine synthesis and release produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). To localize the receptors responsible for the attenuation of MDMA-induced release, 5-HT2 receptor antagonists were infused via the microdialysis probe directly into the brains of awake, freely moving rats before the systemic administration of MDMA. Intrastriatal infusions of the selective 5-HT2 antagonist MDL 100,907 produced a concentration-dependent inhibition of MDMA-induced dopamine release. Similar results were observed with intrastriatal infusions of the 5-HT2 antagonist amperozide. In contrast, infusion of MDL 100,907 into the mid-brain region near the dopaminergic cell bodies was without effect on the MDMA-induced elevation of extracellular dopamine in the ipsilateral striatum. Neither antagonist attenuated basal transmitter efflux nor the MDMA-stimulated release of [3H]dopamine from striatal slices in vitro indicating that the in vivo effect of the antagonists was not due to inhibition of the dopamine uptake carrier. Intrastriatal infusion of tetrodotoxin reduced both basal and MDMA-stimulated dopamine efflux and eliminated the effect of intrastriatal MDL 100,907. The results indicate that 5-HT2 receptors located in the striatum augment the release of dopamine produced by high doses of MDMA. Furthermore, these 5-HT2 receptors appear to be located on nondopaminergic elements of the striatum.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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