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Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice

Julie Salzmann, Cynthia Marie‐claire, Stéphanie Le Guen, Bernárd P. Roques, Florence Noble

British Journal of Pharmacology October 29, 2003 DOI: 10.1038/sj.bjp.0705506 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Male CD-1 mice
Interventions MDMA SL327
Dose 9 mg kg −1 i.p. (MDMA), 50 mg kg −1 i.p. (SL327)
Topics MDMA
Keywords Nucleus accumbens Mapk/erk pathway Caudate nucleus Immediate early gene Conditioned place preference C-fos Putamen Pharmacology Signal transduction Endocrinology
Citations 120
Key findings MDMA-induced reward and locomotor activation depend on the ERK signaling pathway, and MDMA increases immediate early gene transcription in brain reward regions, with ERK involvement specific to the caudate putamen.

Abstract

Little is known about the cellular effects induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy), although changes in gene expression have been observed following treatments with other psychostimulants. Thus, the aim of this study was to investigate in mice, the relationships between the ras‐dependent protein kinase ERK and MDMA‐induced reinforcement using the conditioned place preference (CPP) and locomotor activity measurements. This was completed using real‐time quantitative PCR method by a study of immediate early‐genes (IEGs) transcription known to be involved in neuronal plasticity. A significant CPP was observed after repeated MDMA treatment in CD‐1 mice at a dose of 9 mg kg −1 i.p. but not at 3 and 6 mg kg −1 . This rewarding effect was abolished by the selective inhibitor of ERK activation, SL327 (50 mg kg −1 ; i.p.). Similar results were obtained on MDMA‐induced locomotor activity, clearly suggesting a role of ERK pathway in these behavioral responses. Following acute i.p. injection, MDMA induced a strong c‐fos transcription in brain structures, such as caudate putamen, nucleus accumbens and hippocampus, whereas egr‐1 and egr‐3 transcripts were only increased in the caudate putamen. MDMA‐induced IEGs transcription was selectively suppressed by SL327 in the caudate putamen, suggesting a role for other signaling pathways in regulation of IEGs transcription in the other brain structures. In agreement with these results, MDMA‐induced c‐fos protein expression was blocked by SL327 in the caudate putamen. This study confirms and extends to mice the reported role of ERK pathway in the development of addiction‐like properties of MDMA. This could facilitate studies about the molecular mechanism of this process by using mutant mice. British Journal of Pharmacology (2003) 140 , 831–838. doi: 10.1038/sj.bjp.0705506

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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