Chrysin prevents acute stress-induced anxiety-like, but not despair-like, behavior in a rat model of surgical menopause: Association with Fos-immunoreactivity in the lateral septum.

Low concentrations of ovarian hormones resulting from ovariectomy increase susceptibility to the adverse effects of stress. In rats, long-term ovariectomy enhances anxiety- and despair-like behaviors and reduces Fos immunoreactivity in the lateral septum (LS)-a brain region implicated in the pathophysiology of anxiety and depression, as well as the pharmacologic effects of anxiolytic and antidepressant agents. The flavonoid chrysin has demonstrated anxiolytic- and antidepressant-like effects in preclinical studies; however, its ability to prevent stress-induced behavioral and neurobiological changes in ovariectomized rats remain unknown. Female Wistar rats, 11 weeks post-ovariectomy, were assigned to six groups: control (no manipulation); vehicle; chrysin (0.5, 1, or 2 mg/kg, intraperitoneally), or diazepam (2 mg/kg, intraperitoneally). Treatments were administered for seven consecutive days, and 1 h after the final injection, rats were exposed to a 15-minutes swim-induced stress session. Behavioral outcomes were assessed 24 h later using the elevated plus maze, locomotor activity test, and forced swim test. Fos immunoreactivity in the LS was also quantified. Acute stress increased anxiety- and despair-like behaviors and significantly reduced Fos immunoreactivity in the LS. Chrysin at 1 and 2 mg/kg prevented anxiety-like, but not despair-like behavior, and restored Fos immunoreactivity in the ventral LS. Locomotor activity was unaffected across all groups. These findings suggest that long-term ovariectomy heightens vulnerability to stress-induced anxiety- and despair-like behavior, which may be partially mitigated by chrysin. Although chrysin showed potential as a nonhormonal strategy for managing anxiety associated with surgical menopause, challenges related to its low solubility, poor bioavailability, and limited toxicological data warrant future investigation.