Effects of Ketanserin on Anxiety-Depression-Like Behavior in Female Rats during Key Phases of the Ovarian Cycle

Abstract

The aim of the present work was to assess the effects of chronic administration of NAN-190, a 5-HT1A receptor antagonist (0.1 mg/kg, i.p.), and the 5-HT2A/2C receptor antagonist ketanserin (0.1 mg/kg, i.p.) for 14 days on anxiety and depression-like behavior in female rats during the ovarian cycle. Depression was modeled in rats using the Porsolt test. Levels of anxiety were evaluated using the elevated plus maze test. Chronic ketanserin was found to have antidepressant and anxiolytic effects in rats during estrous phases and proestrus. Administration of NAN-190, conversely, facilitated the development of a more profound state of depression in estrous phases and proestrus. Administration of this substance was followed by clear modulation of anxiety behavior depending on the phase of the estrous cycle: anxiolytic effects were seen when endogenous estrogen levels were high, while anxiogenic effects were seen at low estrogen levels. This is evidence for different levels of involvement of different serotonin receptor subtypes in the mechanisms of anxious-depressive behavior in conditions of a changing hormonal background during the estrous cycle. These data point to a close relationship between the ovarian hormonal and brain serotoninergic systems in the mechanisms of anxiety behavior and depression.