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 via OpenAlex
Summary
AI-generated from the abstractRepeated high doses of MDMA impaired mice's ability to learn and recall an active avoidance task. Pretreatment with a low dose (5 mg/kg) of the endogenous PPAR-α agonist oleoylethanolamide (OEA) partially protected against these deficits, while a higher dose (25 mg/kg) worsened them. MDMA also reduced dopamine transporter (DAT)-binding sites in the brain four days after the last dose, an effect prevented by both OEA doses. Coexpression of tyrosine-hydroxylase and PPAR-α receptors was observed in the striatum and substantia nigra pars compacta, suggesting OEA modulates MDMA-induced cognitive deficits through a DAT-independent mechanism.
Study at a glance
| 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 |
| Citations | 3 |
| Key finding | 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.