Effects of oleoyl-/palmitoyl-ethanolamide in the reduction of cocaine-induced behavioural sensitization and conditioned locomotion in mice

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

San Diego

Congreso; 40th Annual Meeting of the Society for Neuroscience; 2010

Society for Neuroscience (SfN)

Oleoyl-/Palmitoyl-ethanolamide (OEA/PEA) are endogenous lipid mediators capable of activating cellular targets including the endogenous peroxisome proliferator-activated receptor type (PPARalpha) and the transient receptor potential vanilloid type 1 (TRPV1). OEA is an agonist of the acylethanolamides GPR55/GPR119 receptors, and PPARalpha and TRPV1 while PEA is a selective GPR55 agonist that activates PPARalpha. In rodents, OEA is involved in the regulation of lipid metabolism, appetite-suppressing activity and neuroprotection; PEA seems to be related with anti-inflammatory and nociceptive properties. But, the contribution of OEA/PEA to behavioural aspects, such as reward-based behaviours, learning and memory processes, remains largely unknown. We studied the role of OEA/PEA in the regulation of cocaine-induced conditioned locomotion (CL) and behavioural sensitization (BS) in mice. Administration of OEA (5, 20 mg/kg) or PEA (1, 10 mg/kg) during the acquisition of cocaine conditioning did not affect the development of BS or CL. After the cocaine conditioning, a single administration to different doses of OEA (5, 20 mg/kg) and PEA (1, 10 mg/kg) were able to block the development of cocaine sensitization. But while PEA (1, 10 mg/kg) did not influence, OEA (5, 20 mg/kg) reduced the expression of CL. Surprisingly after 7 weeks of cocaine sensitization, animals treated with acute PEA (10 mg/kg) before CL or chronic co-administration PEA (10 mg/kg) + cocaine (20 mg/kg) showed an impairment of recovery to CL test in the open field; whereas, animals treated with chronic cocaine (20 mg/kg) did not disrupt the performance of the CL response. These results suggest that PEA administration can disrupt the long-term recovery of hippocampal-dependent consolidation in the CL response induced by cocaine. In conclusion, our findings indicate that OEA/PEA develop neuromodulatory properties as activators of novel cannabinoid receptors and PPARalpha in the brain, supplying a potential target for the treatment of cocaine-induced behavioural responses in psychostimulants addiction.