3,4-methylenedioxymethamphetamine (‘Ecstasy’) promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals

H Kenneth Kramer; Jose C Poblete; Efrain C. Azmitia

doi:10.1016/0006-8993(95)00199-z

3,4-methylenedioxymethamphetamine (‘Ecstasy’) promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals

H Kenneth Kramer, Jose C Poblete, Efrain C. Azmitia

Brain Research May 1, 1995 DOI: 10.1016/0006-8993(95)00199-z (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	In vivo animal study Peer reviewed
Population	Rats (cortical tissue; specific strain, sex, and number not stated)
Interventions	MDMA p-chloroamphetamine (PCA)
Dose	20 mg/kg (two injections 10 h apart; also 8 x 20 mg/kg)
Duration	Up to 5 days post-treatment
Measures	membrane-bound PKC density, [3H]phorbol 12,13 dibutyrate ([3H]PDBu) binding affinity
Topics	MDMA Serotonin
Citations	22
Key points	MDMA increased membrane-bound PKC density in rat cortex by 48.0% after two 20 mg/kg injections and produced a lasting increase (up to 5 days) after eight injections, without altering ligand affinity. Prior destruction of cortical serotonin nerve terminals with p-chloroamphetamine blocked this effect, which the authors argue shows that viable serotonin uptake sites are required for MDMA-induced PKC translocation and that prolonged kinase activation may contribute to MDMA's serotonergic neurotoxicity.

Abstract

The metabolic effects of the neurotoxic, ring-substituted amphetamine 3,4-methylenedioxy-methamphetamine (MDMA or 'Ecstasy') were examined in vivo. In this study, we focused on the ability of MDMA to induce a translocation of the calcium and phospholipid-dependent protein kinase C (PKC) from the cytosol to the cortical plasma membrane. Two injections of MDMA (20 mg/kg; 10 h apart; s.c.) increased the density of membrane bound PKC sites by 48.0% over saline treated animals without mediating a significant change in ligand ([3H]phorbol 12,13 dibutyrate; [3H]PDBu) affinity. Longer drug treatments (8 x 20 mg/kg) induced a lasting (up to 5 days post-treatment) increase in the density of membrane-bound PKC. Prior destruction of cortical 5-HT nerve terminals with p-chloroamphetamine (PCA) prevents this effect and suggests that viable 5-HT uptake sites are essential for MDMA-induced PKC translocation. These results demonstrate that MDMA-induced PKC translocation is mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.

Comparable studies

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

Study	Year	Design
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

Citations in the library

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