Polygala tenuifolia prevents anxiety-like behaviors in mice exposed to repeated restraint stress

Abstract

The pathophysiology underlying anxiety disorders involves stress and associated increases in glucocorticoid levels in the blood. The present study investigated the effects of the administration of the crude extract of Polygala tenuifolia (EPT) on repeated restraint stress–induced anxiety-like behavioral responses in mice. Additionally, possible changes in the central noradrenergic and brain-derived neurotrophic factor (BDNF)–signaling systems were assessed in the hippocampus of these mice. For 14 consecutive days, mice were orally administrated EPT (50 or 250 mg/kg) 30 min prior to the restraint stress procedure (2 h/day). Dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis in response to the repeated restraint stress was confirmed by measuring serum levels of corticosterone and the expression of corticotrophin-releasing factor in the hypothalamus. Compared with control subjects, the daily administration of higher doses of EPT (250 mg/kg) increased open-arm exploration in an elevated plus maze and the total number of line crossings in an open-field test. EPT also reversed the increased expression of tyrosine hydroxylase in the locus coeruleus and the decreased expression of BDNF mRNA in the hippocampus. Together, these findings demonstrate that the administration of EPT prior to repeated restraint stress significantly reduced anxiety-like behaviors in mice. These changes were associated with a modification of the central noradrenergic system and the upregulation of BDNF expression, which in turn attenuated activity in the HPA axis.