BEHAVIORAL EFFECTS OF ACUTE ADMINISTRATION OF THE PPAR-α AGONIST PALMITOYLETHANOLAMIDE IN RATS

N-palmitoylethanolamide (PEA), the amide of palmitic acid and ethanolamine is an endogenous ligand of peroxisome proliferator-activated receptor-alpha (PPAR-α) that possesses effects on metabolism, feeding, inflammation and pain (Pistis and Melis, 2010). Our previous investigations have shown that PEA induces a dose-dependent antidepressant-like effect with a behavioral profile similar to that of the tricyclic antidepressant amitriptyline (unpublished data). This effect was reversed by the PPAR-α antagonist MK886, showing that it is specifically mediated via PPAR-α activation. Scope of this study was to characterize the pharmacological effects of an acute intraperitoneal (ip) administration of PEA (1 and 2 mg/kg) on anxiety, social interactions and spontaneous motor activity. Anxiety-like behavior has been evaluated by means of the elevated plus maze (EPM) test, that is based on the conflict between the animal’s instinct to explore its environment and its innate fear for open spaces: classical anxiolytic drugs elevate the time spent in the open compartments and the number of entries (Pellow and File, 1986). In the EPM test, we found that PEA (1 and 2 mg/kg ip) does not modify the percentage of either the open arm entries and the time spent in the open arms as compared with vehicle-treated controls. Social behavior was evaluated by means of the social interactions (SI) test that could provide another measure of anxiety (File and Seth, 2003), with time spent in social interactions being usually elevated by anxiolytic drugs. Animals acutely treated with 1 mg/kg (ip) of PEA significantly decrease the total time spent in social interaction but do not modify the total numbers of contacts with respect to vehicle-treated controls thus revealing an anxiogenic-like response. In the spontaneous motor activity test, evaluated using the Digiscan Animal Activity Analyser (Omnitech Electronics, USA), no difference has been found between treatment groups. Our results suggest an anxiogenic-like effect of PEA after acute administration, in agreement with the notion that several antidepressants show an anxiogenic profile after acute treatment. On the basis of these results it will be important to investigate the pharmacological and behavioral profile of PEA on anxiety–like behavior after chronic regime of treatment. File and Seth (2003). Eur J Pharmacol 463: 35-53. Pellow et al. (1986). Pharmacol Biochem Behav 24: 525-9. Pistis and Melis (2010). Curr Med Chem 17:1450-67