Cocaine-induced behavioural sensitization effects are reduced by oleoyl- and palmitoylethanolamide in mice

BLANCO CALVO, EDUARDO; LUQUE ROJAS, MARÍA JESÚS; GALEANO, PABLO; MILEI, JOSÉ; CAPANI, FRANCISCO; SANTÍN NUÑEZ, LUIS JAVIER; RODRÍGUEZ DE FONSECA, FERNANDO

Amsterdam

Congreso; 7th Forum of European Neuroscience; 2010

Federation of European Neuroscience Societies (FENS)

Oleoyl- and Palmitoylethanolamide (OEA and PEA) are two endogenous lipid mediators capable of activating cellular targets, including the peroxisome proliferator-activated nuclear receptor type alpha (PPARalpha) and the transient receptor potential vanilloid type 1 (TRPV1). OEA is an agonist of the acylethanolamide GPR55 and GPR119 receptors, as well as of the PPARalpha and TRPV1 receptors. Similarly, PEA is a selective agonist of GPR55 that directly activates PPARalpha. In rodents, OEA is involved in the control of lipid metabolism, feeding behaviour, analgesia and neuroprotection. PEA seems to possess antiinflammatory, antinociceptive and anticonvulsive effects. Nevertheless, the contribution of OEA and PEA to behavioural aspects, such as reward-based behaviours, learning and memory processes, remains unclear. In this study, we examined the role of OEA and PEA in the regulation of cocaine-induced conditioned locomotion and behavioural sensitization in mice. A single coadministration of OEA (5 and 20 mg/kg) and cocaine (20 mg/kg) reduced locomotor activating effects, while OEA single injection (5 and 20 mg/kg) produced only mild hypokinesia. However, coadministration of PEA (1 & 10 mg/kg) and cocaine (20 mg/kg) did not attenuate hyperlocomotor activity, and PEA alone (1 and 10 mg/kg) did not yield hypolocomotor effects. The doses of OEA and PEA used during cocaine conditioning did not affect the development of behavioural sensitization or conditioned locomotion. After cocaine conditioning, a single administration of different doses of OEA (5 and 20 mg/kg) or PEA (1 and 10 mg/kg) was able to block the development of cocaine sensitization. Finally, PEA (1 and 10 mg/kg) did not influence conditioned locomotion, whereas OEA (5 and 20 mg/kg) reduced its expression. In conclusion, our findings indicate that both OEA and PEA possess neuromodulatory properties throughout the activation of novel cannabinoid and PPARalpha receptors in the brain, and represent potential targets for the treatment of adverse behavioural responses associated with cocaine addiction. Supported by grant P07-CTS-03324 (to F. R. F) from the CICE, Andalusian; grant PCI-A/023328/09 (to E. B. C.) from the MAEC, Spain. E. B. C. is a recipient of a postdoctoral fellowship (Juan de la Cierva) from the MICINN, Spain.