Serotonin participates almost in all vital functions of the body and plays a critical role in the regulation of many forms of behavior.

In line with modern concepts based pathophysiology of affective disorders leading role belongs to reduce noradrenergic and serotonergic neurotransmission in the brain. It is well known that estrogens have a controlling influence on the serotonergic system in the brain, as well as the mechanisms involved in the development of bipolar disorder, anxiety and depression.

Given the close interaction between the ovarian hormonal and serotonergic neurotransmitter systems is of interest to evaluate the role of 5-HT2 receptor subtypes in depression-like behavior in female rats under hypoestrogenism due to surgical ovariectomy. The aim of the present work was to estimate influence of chronic administration of 5-НТ2B/2C receptors agonist – m-CPP (0,5 mg/kg, i.p.) and 5-НТ2А/2C receptors antagonist – ketanserine (0,1 mg/kg, i.p.) alone or in a combination with 17β-estradiol (0,5 μg on each animal, i.m.) for 14 days on depressive behavior and monoamines levels in hippocampus in the adult ovariectomized female rats.

Reseach has been executed on 80 white adult Wistar female rats weighing 180–200 g. Animals were kept in natural light and maximal standardization of temperature and nutrient regimes with free access to food and water. All of the studies have been conducted in the morning (9.00–12.00).

Testing of depression-like behavior in rats was carried out in Porsolt despair test. Monoamines levels and its metabolites were determined by using HPLC.

The animals were divided into the following groups: 1 – intact females in the stage of diestrus treated saline solution (control 1); 2 – intact females in the stage of diestrus treated m-CPP (Sigma, USA) (0.5 mg/kg, i.p.); 3 – intact females in the stage of diestrus treated ketanserin (Sigma, USA) (0.1 mg/kg, i.p.); 4 – ovariectomized females treated oil solvent, i.m.(control 2); 5 – ovariectomized females treated 17β-estradiol (Sigma, USA) (0.5 mg per pet, i.m.); 6 – ovariectomized females treated daily m-CPP; 7 – ovariectomized females treated daily m-CPP, in combination with 17β-estradiol in the same dose, which have introduced the ovariectomized females; 8 – ovariectomized females treated daily with ketanserin; 9 – ovariectomized females treated daily with ketanserin, in combination with 17β-estradiol in the same dose, which have introduced the ovariectomized females. All the drugs were in 2 weeks after surgery. Period of introduction of pharmacological substances was 14 days for both intact and for the ovariectomized rats.

As intact females rats under diestrus were used, because it is a physiological condition that is characterized by hormonal balance.

Character exchange hippocampal monoamines were determined before and after the completion of behavioral experiments.

It was established that chronic ketanserine administration rendered antidepressant effect in ovariectomized rats. Chronic ketanserine administration in combination with 17β-estradiol in ovariectomized females potentiated antidepressant action. The antidepressant effect of ketanserine in ovariectomized rats correlated in rats with restoration of noradrenergic, serotonergic, dopaminergic neurotransmissions in hippocampus. The data obtained indicate close interaction between ovary hormonal and serotonergic systems of the brain in mechanisms of depression.

Ключові слова: m-CPP, ketanserine, ovariectomy, depression, HPLC, monoamines, estrogen

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