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Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARα receptor-independent mechanism

  1. Ainhoa Bilbao1,†,*,
  2. Eduardo Blanco2,3,†,
  3. María Jesús Luque-Rojas2,
  4. Juan Suárez2,
  5. Ana Palomino2,
  6. Margarita Vida2,
  7. Pedro Araos2,
  8. Francisco J. Bermúdez-Silva2,
  9. Emilio Fernández-Espejo4,
  10. Rainer Spanagel1,
  11. Fernando Rodríguez de Fonseca2,*

Article first published online: 19 NOV 2012

DOI: 10.1111/adb.12006

Issue

Addiction Biology

Addiction Biology

Volume 18, Issue 1, pages 78–87, January 2013

Additional Information

How to Cite

Bilbao, A., Blanco, E., Luque-Rojas, M. J., Suárez, J., Palomino, A., Vida, M., Araos, P., Bermúdez-Silva, F. J., Fernández-Espejo, E., Spanagel, R. and Rodríguez de Fonseca, F. (2013), Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARα receptor-independent mechanism. Addiction Biology, 18: 78–87. doi: 10.1111/adb.12006

Author Information

  1. 1

    Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Germany

  2. 2

    Laboratorio de Medicina Regenerativa, IBIMA-Hospital Carlos Haya, Spain

  3. 3

    Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Spain

  4. 4

    Departamento de Fisiología, Facultad de Medicina de Sevilla, Spain

  1. †

    These authors contributed equally to this work.

*Correspondence to: Ainhoa Bilbao, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, 68159 Mannheim, Germany. E-mail: ainhoa.bilbao@zi-mannheim.de and Fernando Rodríguez de Fonseca, Fundación IMABIS, Laboratorio de Medicina Regenerativa, Hospital Regional Universitario Carlos Haya, 29010 Málaga, Spain. E-mail: fernando.rodriguez@fundacionimabis.org

  1. †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 25 DEC 2012
  2. Article first published online: 19 NOV 2012

Funded by

  • Consejería de Innovación, Ciencia y Empresa of the Regional Andalusian government. Grant Number: P07-CTS-03324
  • Spanish Health Institute Carlos III. Grant Number: RD06/0001/0000
  • Plan Nacional sobre Drogas 2009/2011. Grant Number: 049/2009
  • Andalusian Health Service . Grant Number: SAS 111224
  • Plan Andaluz de Investigación. Grant Number: BIO127
  • Ministerio de Sanidad (Plan Nacional sobre Drogas. Grant Number: 2009I039
  • Instituto Carlos III. Grant Number: RD06/001/002
  • National System of Health (Instituto de Salud Carlos III. Grant Number: CD08/00203

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Keywords:

  • cocaine;
  • knockout;
  • motor sensitization;
  • oleoylethanolamide;
  • PPARα;
  • reinforcement

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.

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