Neurohormonal mechanisms of the antidepressant effect of ketanserin in ovariectomized rats

In the present study we investigated the effects of chronic administration of m-CPP (0.5 mg/kg, i.p.), a 5-HT_2B/2C receptor agonist, and ketanserin (0.1 mg/kg, i.p.), a 5-HT_2A/2C receptor antagonist, alone or in a combination with 17β-estradiol (0.5 μg per animal, i.m.) over 14 days on depressive behavior and the concentration of different monoamines in the hippocampus in adult ovariectomized (OVX) female rats. Depression-like behavior was assessed using the Porsolt’s test. The concentrations of monoamines and their metabolites were determined using HPLC. We found that chronic ketanserin administration has an antide-pressant effect in OVX rats. Chronic ketanserin administration in combination with 17β-estradiol in OVX females potentiated antidepressant action. The antidepressant effect of ketanserin in OVX rats correlated with the restoration of noradrenergic, serotonergic, and dopaminergic neurotransmission in the hippocampus. Our data indicate a close interaction between the ovary hormonal and serotonergic systems of the brain in mechanisms of depression.