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Effects of the endogenous PPAR‐α agonist, oleoylethanolamide on MDMA‐induced cognitive deficits in mice

Ainhoa Plaza‐zabala, Fernando Berrendero, Juan Suárez, Francisco J. Bermúdez‐silva, Emilio Fernández‐espejo, Antonia Serrano, Francisco Javier Pavón, Loren H. Parsons, Fernando Rodrı́guez de Fonseca, Rafaël Maldonado, Patricia Robledo

Synapse December 22, 2009 DOI: 10.1002/syn.20733 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Mice
Interventions Oleoylethanolamide MDMA
Dose OEA 5 mg/kg and 25 mg/kg; MDMA 30 mg/kg
Duration 4 consecutive days of treatment, followed by 2 weeks of training, then a 5-day rest period before recall
Topics MDMA
Keywords Agonist Pars compacta Dopamine transporter Pharmacology Striatum Amphetamine Endocrinology Substantia nigra Receptor
Citations 3
Key findings Oleoylethanolamide at 5 mg/kg ameliorated, but at 25 mg/kg worsened, MDMA-induced deficits in learning and recall of an active avoidance task in mice.

Abstract

Abstract MDMA (3,4‐Methylenedioxymethamphetamine) is an amphetamine derivative widely used for recreational purposes. We have recently shown that repeated treatment with high doses of MDMA‐induced impairments in the acquisition and recall of an active avoidance task in mice. In this study, we examined whether the endogenous peroxisome proliferator‐activated receptor‐α (PPAR‐α) agonist, oleoylethanolamide (OEA) protects against these MDMA‐induced deficits. Mice were pretreated twice a day with OEA (0, 5, and 25 mg/kg) 30 min before an injection of MDMA (30 mg/kg) or saline during four consecutive days. Twenty‐four hours after the last treatment, animals were trained in an active avoidance task for two consecutive weeks. After a 5‐day resting period, a recall session was performed. Mice treated with MDMA showed reduced learning and recall of the task when compared with saline‐treated controls. OEA at 5 mg/kg ameliorated and at 25 mg/kg worsened this deficit. Dopamine transporter (DAT)‐binding sites significantly decreased 4 days after the last MDMA administration and pretreatment with both doses of OEA prevented this effect. In immunohistochemical studies, coexpression of tyrosine‐hydroxylase and PPAR‐α receptors was observed in the striatum and substantia nigra pars compacta of mice. These results suggest that OEA administration can modulate the cognitive deficits induced by MDMA in a DAT‐independent manner. Synapse 64:379–389, 2010. © 2009 Wiley‐Liss, Inc.

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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