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.