N-palmitoylethanolamide Treatment Exhibits Antidepressant Effects In A Mouse Model Of Anxiety/Depressive Like Behavior

¹ Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy
² IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy

Palmitoylethanolamide (PEA) is a member of fatty-acid ethanolamide family. This endocannabinoids is an endogenous neuromodulator with a broad spectrum of pharmacological properties, including analgesic, anti-inflammatory, anticonvulsant and antiproliferative effects. The aim of this study was to investigate the effects of PEA (5,10 mg/kg, i.p.) in the neural development in the adult hippocampus and the behavioral changes in a depressive-like state. The antidepressant-like effect of PEA was evaluated by using a mouse model of anxiety/depressive-like behavior induced by chronic corticosterone treatment. 129 Sv/Ev mice were administered corticosterone for 7 wk, and behavioral tests as novelty-suppressed feeding, open field, forced swim were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by 5-bromo-2- deoxyuridine and doublecortin immunohistochemistry techniques. Golgi- impregnated method was used to evaluate the changes of dendritic spines in DG neurons. The depressive-like state caused by corticosterone treatment was reversed by exogenous administration of PEA for 3 wk; the proliferation of progenitor cells was reduced under chronic corticosterone treatment, whereas treatment with PEA prevented the corticosterone-induced reduction in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density, which was ameliorated by PEA administration. These findings suggest that PEA may play an important role in the near future in the treatment of depression.