Antidepressant-Like Activity of Naringenin, an Important Agro-Industrial Resource, Complexed with β‑Cyclodextrin

The objective of this work was to investigate the effect on the central nervous system (CNS) of naringenin (NR) and of the inclusion complex obtained with its incorporation into β-cyclodextrin (NR-βCD) in mice, using experimental models. The possible participation of the monoaminergic system in the antidepressant activity of NR was also studied. NR and NR-βCD, when administered acutely (20 and 40 mg/kg, p.o.), produced a significant reduction in the immobility time (p < 0.05), an effect comparable to imipramine (30 mg/kg, p.o.). The reduction in immobility time observed after NR treatment (20 mg/kg, p.o.) was prevented by pretreatment with haloperidol (0.2 mg/kg, i.p., a D₂ receptor antagonist) and yohimbine (Yob) (1 mg/kg, i.p., an α₂-adrenoceptor antagonist), but not with ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). In summary, NR and NR-βCD produced an antidepressant-like effect with no change in locomotor activity. Furthermore, this anti-immobility effect seems to be mediated by interaction with dopaminergic and noradrenergic systems.