Effects of the endogenous PPAR-alpha agonist, oleoylethanolamide on MDMA-induced cognitive deficits in mice.
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.
Plaza-Zabala
Ainhoa
A
Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003Barcelona, Spain.
Berrendero
Fernando
F
Suarez
Juan
J
Bermudez-Silva
Francisco Javier
FJ
Fernandez-Espejo
Emilio
E
Serrano
Antonia
A
Pavon
Francisco-Javier
FJ
Parsons
Loren H
LH
De Fonseca
Fernando Rodriguez
FR
Maldonado
Rafael
R
Robledo
Patricia
P
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
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