The antidepressant effect of a compound formed by co-ultramicronized palmitoylethanolamide (PEA) and
luteolin (PEA+luteolin) was investigated in a mouse model of anxiety/depressive-like behavior. 129Sv/Ev mice were
subjected to 6 weeks of corticosterone administration, and then behavior, neurogenesis, neuroplasticity, neurotrophic and
apoptotic proteins expression were evaluated. The effect of PEA+luteolin compound treatment (1mg/kg, i.p.), on
depression-like behaviour was assessed using different paradigms such as open field, novelty suppressed feeding, forced
swim test and elevated plus maze. In particular in the open field, novelty suppressed feeding and elevated plus maze the
time spent in the open arm was employed as an indicator of anxiety; forced swim test was used to evaluate the
antidepressant capacity of PEA+luteolin on immobility time as an indicator of depression. Adult hippocampal
neurogenesis and neuroplasticity were evaluated by immunohistochemical techniques; brain-derived neurotrophic factor
and apoptotic protein (Bax and Bcl2) expression were studied by immunostaining and Western blot analysis. For the first
time we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect a low dose and may be
considered as a novel therapeutic strategy in depression.
Keywords: Antidepressant, behavior, depression, inflammation, mice, neurogenesis.
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