Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice

Abstract

Quercetin is a bioflavonoid reported to produce variety of behavioral effects like anxiolytic, antidepressant, etc. Recent gathering evidences indicated that quercetin attenuates stress-induced behavioral and biochemical effects. It also decreases CRF expression in the brain. As CRF is commonly implicated in the high-anxiety and depression, we hypothesized that quercetin may involve CRF in its anxiolytic- and antidepressant-like effects. To support such possibility, we investigated the influence of quercetin on CRF or CRF antagonist (antalarmin) induced changes in social interaction time in social interaction test, and immobility time in forced swim test. Results indicated that quercetin (20–40 mg/kg, p.o.) or antalarmin (2–4 µg/mouse, i.c.v.) dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and antidepressant-like effect. These effects were comparable with the traditional anxiolytic (diazepam, 1-2 mg/kg, i.p.) and antidepressant (fluoxetine, 10–20 mg/kg, i.p.) agents. Administration of CRF (0.1 and 0.3 nmol/mouse, i.c.v.) produced just opposite effects to that of quercetin on these parameters. Further, it was seen that pretreatment with quercetin (20 or 40 mg/kg, p.o.) dose dependently antagonized the effects of CRF (0.1 or 0.3 nmol/mouse, i.c.v.) in social interaction and forced swim test. The sub-effective dose of antalarmin (1 µg/mouse) when administered along with the sub-effective dose of quercetin (10 mg/kg) produced significant anxiolytic-and antidepressant-like effect. These observations suggest reciprocating role of quercetin on the CRF-induced anxiogenic and depressant-like effects.