title: Effects of the endogenous PPAR-alpha agonist, oleoylethanolamide on MDMA-induced cognitive deficits in mice.
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-alpha (PPAR-alpha) 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-alpha 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.
authors.affiliation: Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003Barcelona, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Plaza-Zabala
authors.forename: Fernando
authors.initials: F
authors.lastname: Berrendero
authors.forename: Juan
authors.initials: J
authors.lastname: Suarez
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Bermudez-Silva
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Espejo
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Pavon
authors.forename: Loren H
authors.initials: LH
authors.lastname: Parsons
authors.forename: Fernando Rodriguez
authors.initials: FR
authors.lastname: De Fonseca
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Patricia
authors.initials: P
authors.lastname: Robledo
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D006213:Hallucinogens / Q000009:adverse effects*; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D063388:Endocannabinoids; D006213:Hallucinogens; D018697:Nootropic Agents; D009829:Oleic Acids; D047493:PPAR alpha; C488250:oleoylethanolamide; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine