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Effects of the endogenous PPAR‐α agonist, oleoylethanolamide on MDMA‐induced cognitive deficits in mice
Author(s) -
PlazaZabala Ainhoa,
Berrendero Fernando,
Suarez Juan,
BermudezSilva Francisco Javier,
FernandezEspejo Emilio,
Serrano Antonia,
Pavon FranciscoJavier,
Parsons Loren H.,
De Fonseca Fernando Rodriguez,
Maldonado Rafael,
Robledo Patricia
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20733
Subject(s) - mdma , agonist , pars compacta , dopamine transporter , pharmacology , striatum , amphetamine , dopamine , endocrinology , medicine , psychology , substantia nigra , chemistry , receptor , dopaminergic
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.