title: Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARα receptor-independent mechanism.
abstract: Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARα) to exert their biological functions, which include the regulation of appetite and metabolism. Increasing evidence also suggests that OEA may participate in the control of reward-related behaviours. However, direct experimental evidence for the role of the OEA-PPARα receptor interaction in drug-mediated behaviours, such as cocaine-induced behavioural phenotypes, is lacking. The present study explored the role of OEA and its receptor PPARα on the psychomotor and rewarding responsiveness to cocaine using behavioural tests indicative of core components of addiction. We found that acute administration of OEA (1, 5 or 20 mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARα receptor knockout mice showed normal sensitization, although OEA was capable of reducing behavioural sensitization with fewer efficacies. Furthermore, conditioned place preference and reinstatement to cocaine were intact in these mice. Our results indicate that PPARα receptor does not play a critical, if any, role in mediating short- and long-term psychomotor and rewarding responsiveness to cocaine. However, further research is needed for the identification of the targets of OEA for its inhibitory action on cocaine-mediated responses.
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Germany. ainhoa.bilbao@zi-mannheim.de
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Bilbao
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Luque-Rojas
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.forename: Ana
authors.initials: A
authors.lastname: Palomino
authors.forename: Margarita
authors.initials: M
authors.lastname: Vida
authors.forename: Pedro
authors.initials: P
authors.lastname: Araos
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bermúdez-Silva
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernández-Espejo
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D063388:Endocannabinoids; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D012054:Reinforcement, Psychology; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D063388:Endocannabinoids; D009829:Oleic Acids; D047493:PPAR alpha; C488250:oleoylethanolamide; D003042:Cocaine