Effects of 8-OH-DPAT and NAN-190 on anxiety behavior, monoamine metabolism, and the level of sex hormones in female rats during the estrus cycle

Abstract

In this study, we performed a comparative analysis of the effects of chronic administration of an agonist of 5-HT_1A receptors, 8-OH-DPAT, (0.05 mg/kg, subcutaneously) and an antagonist of 5-HT_1A receptors, NAN-190, (0.1 mg/kg, intraperitoneally) for 14 days on the anxiety behavior, monoamine metabolism in the hippocampus and amygdala, and the level of sex hormones in the blood of adult female rats during the estrus cycle. Anxiety behavior was tested in an elevated X-maze. The level of monoamines and their metabolites was evaluated using HPLC with an electrochemical detector; the content of sex hormones in the blood was measured using an enzyme immunoassay. We found that chronic administration of 8-OH-DPAT has an anxiolytic effect in rats in estrus and proestrus. After treatment with NAN-190, we found clear modulation of anxiety behavior that depended on the phase of the estrus cycle, an anxiolytic effect at a high level of endogenous estrogens and an anxiogenic effect at a low level of estrogens. The anxiolytic effect of 8-OH-DPAT in female rats was accompanied by its suppressive influence on the pituitary-ovarian and noradrenergic systems and by its activating effect on the dopaminergic system of the brain. In contrast, the behavioral effects of NAN-190 in female rats during key phases of the estrus cycle corresponded to its stimulating effect of the pituitary-ovarian system and the absence of any effect on the monoaminergic systems of the brain. These data suggest that the mechanisms of anxiety include tight interaction between the ovarian hormonal system and the serotonergic brain system.