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Examination of the action of 3,4-methylenedioxymethamphetamine on rat A10 dopamine neurons

Andrew N. Gifford, Yoshio Minabe, Alon Toor, Rex Y. Wang, Charles R. Ashby

Synapse May 1, 1996 DOI: 10.1002/(sici)1098-2396(199605)23:1<52::aid-syn6>3.0.co;2-g (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Extracellular single cell recording study in anesthetized rats Peer reviewed
Population Chloral hydrate anesthetized male rats
Interventions MDMA (+)-MDMA (-)-MDMA p-chlorophenylalanine (PCPA) L-DOPA
Topics MDMA
Citations 7
Key points The authors report that (+/-)-MDMA and (+)-MDMA inhibit the firing of most A10 dopamine neurons in rats, while (-)-MDMA does not. They conclude that this inhibition appears to be mediated by dopamine rather than serotonin, since it was blocked by the dopamine synthesis inhibitor AMPT but not by the serotonin synthesis inhibitor PCPA.

Abstract

Extracellular single cell recording was used to examine the effect of intravenous administration of (-), (+), and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) on A10 dopamine (DA) neurons in chloral hydrate anesthetized male rats. Both (+/-)-MDMA and (+)-MDMA inhibited the firing rate of most (79%) A10 DA cells. By contrast, (-)-MDMA induced either no effect or a slight increase in the firing rate of these cells. Analysis of the effects of (+/-)-MDMA on the firing pattern of the DA cells revealed on overall decrease in the percentage of spikes in bursts but both increases and decreases were seen in the coefficient of variation of interspike intervals. To determine the contribution of 5-HT and DA to the (+/-)-MDMA-induced inhibition of A10 DA cells rats were pretreated either with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) or the DA synthesis inhibitor alpha-methyl-p-tyrosine (AMPT). Pretreatment of rats with PCPA did not reduce the ability of (+/-)-MDMA to inhibit the DA cells. However, in rats pretreated with AMPT, the (+/-)-MDMA-induced inhibition was blocked and some cells (44%) showed instead an increase in firing rate following administration of (+/-)-MDMA. The administration of l-3,4-dihydroxyphenylalanine (L-DOPA) to AMPT-treated rats rapidly restored the inhibition of cell firing by (+/-)-MDMA. In conclusion, the results reported here demonstrate that MDMA has an overall inhibitory effect on A10 DA cells. Despite MDMA's greater potency in releasing 5-HT compared to DA, the inhibitory effect of this drug on A10 DA cells appears to be mediated by the latter transmitter.

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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