Yu. O. Fedotova

Effects of 8-OH-DPAT and NAN-190 on Anxious-Depressive-Like Behavior of Female Rats during the Estrous Cycle

We studied the effect of chronic administration of 5-HT1A-receptor agonist 8-OH-DPAT (0.05 mg/kg subcutaneously) or antagonist NAN-190 (0.1 mg/kg intraperitoneally) for 14 days on anxious-depressive-like behavior of female rats during the key phases of the estrous cycle. Chronic administration of NAN-190 during the estrus phase produced an anxiogenic effect, while its administration during proestrus phase induced an anxiolytic effect. Administration of 8-OH-DPAT had no effect on anxiety level, but produced a pronounced antidepressive effect irrespective of the phase of the estrous cycle.

Blockade of 5-HT2A/2C-Type Receptors Impairs Learning in Female Rats in the Course of Estrous Cycle

Were studied the effects of chronic administration (14 days) of agonist of 5-HT2B/2C serotonin receptors m-CPP (0.5 mg/kg subcutaneously) and agonist of 5-HT2A/2C serotonin receptors ketanserin (0.1 mg/kg intraperitoneally) on conditioned reactions in female rats in different phases of the estrous cycle. Passive avoidance (PA) paradigm and Morris water maze were used as behavioral tests. Chronic administration of m-CPP did not affect PA retrieval during the proestrus and estrus phases, but improved the dynamics of spatial learning in Morris water maze in comparison with control rats. Chronic administration of ketanserin uniformly impaired processes of spatial and nonspatial learning in female rats irrespective to the phase of the estrous cycle. A modulating role of 5-HT2A/2C and 5-HT2B/2C serotonin receptors in process of learning in female rats during the key phases of the estrous cycle was demonstrated.

Formation of an Anxious-Depressive State in an Experimental Model of Post-Traumatic Stress Disorder in Prenatally Stressed Female Rats

The characteristics of the formation of a pathological state in an experimental model of post-traumatic stress disorder (PTSD) in adult female rats born to mothers subjected to daily restraint stress during the last third of pregnancy were studied. Both control and prenatally stressed female rats developed a pathological state after severe combined stress and subsequent restress, with long-lasting increases in anxiety and enhanced fast feedback inhibition of stress-related hypophyseal-adrenocortical system (HAS) activity. However, while development of the pathological state in control animals progressed to the anxiety type, prenatally stressed animals developed not only anxiety, but also increased depression-like behavior, i.e., an anxiety-depression disorder developed. These data are interpreted in the light of the interaction between the characteristics of HAS activity in prenatally stressed females and the predisposition of these animals to developing poststress pathology.

Specific monoamine exchange in the brains of young and aged male rats with hypothyroidism

We analyzed monoamine exchange in different brain structures of young (2-month-old) and aged (22–24 month-old) male rats under conditions of thyroid hormone (TH) deficit or 14-day-long intraperitoneal (T3) administration of triiodothyronine at a dose of 70 μg/kg. The contents of monoamines and their metabolites were assayed using HPLC with an electrochemical detector. In the brain structures directly related to animal behavior a TH deficit resulted in changes in monoamines, which depended on the ages of the rats. During experimental hypothyroidism, the most substantial changes in the contents and turnover of norepinephrine, dopamine, and serotonin were observed in the brains of young male rats. In aged animals, a TH deficit increased impairments in neurotransmitter exchange. Substitutive T3 administration did not improve monoamine exchange in the brain structures of young male rats with hypothyroidism. In the aged rats with hypothyroidism, T3 administration restored monoamine exchange only in the hippocampus but not in other brain structures.

Effects of SCH-23390 and Sulpiride on Active Avoidance in Ovariectomized Rats Treated with a Low Dose of 17β-Estradiol

We studied the effects of dopamine D1/D2 receptor antagonists on the dynamics of acquisition and extinction of active avoidance responses and open field behavior in ovariectomized female rats. Dopamine D1 receptor antagonist SCH-23390 (0.1 mg/kg intraperitoneally) and dopamine D2 receptor antagonist sulpiride (10.0 mg/kg intraperitoneally) were administered chronically (14 days) either alone or in combination with a low dose of 17β-estradiol (0.5 μg per rat subcutaneously) to females after ovariectomy. It was found that SCH-23390 in combination with a low dose of 17β-estradiol completely restored impaired conditioning and retention of a conditioned avoidance response in ovariectomized animals. Simultaneous correction of behavioral patterns in the open field test was also observed in ovariectomized females receiving SCH-23390. Sulpiride injected alone or in combination with low dose of 17β-estradiol did not correct conditioning and reproduction of active avoidance response in females with estrogen deficiency and did not significantly affect animal behavior. The results indicate positive effect of dopamine D1 receptor blockade on active learning under conditions of estrogen deficiency.

Characteristics of Depressive-Like Behavior of Prenatally Stressed Male Rats with Androgen Deficiency

Characteristics of depressive-like behavior of male rats with androgen deficiency born by mothers subjected to prenatal stress during pregnancy were assessed by using Porsolt tests and open-field tests. The level of depression-like behavior in prenatally stressed males increased more intensively than in non-stressed gonadectomized males. Chronic administration of testosterone propionate (0.5 mg/kg, intramuscularly, for 14 days) increased depressive behavior in prenatally stressed gonadectomized males in contrast to its antidepressant effect in nonstressed gonadectomized rats. Prenatal stress considerably exacerbated depressive behavior of male rats under conditions of androgen deficiency and abolished the antidepressant effect of exogenously administered testosterone propionate.

Effects of Prenatal Stress on the Activity of the Pituitary-Ovarian System in Female Rats

The comparative analysis of hormonal status was performed in mature female rats with experimental defi ciency of estrogens, which mothers were exposed to stress during pregnancy. High levels of follicle-stimulating hormone and luteinizing hormone, and signifi cantly lower amount of estradiol were observed in intact prenatally stressed females in comparison with intact non-stressed female rats. The increase in the levels of follicle-stimulating hormone and luteinizing hormone, and the decrease in estradiol concentration were more pronounced in blood serum of prenatally stressed ovariectomized rats as distinct from intact non-stressed and prenatally stressed female rats, and non-stressed ovariectomized female rats. We can conclude that prenatally stressed ovariectomized rats were characterized by an increased sensitivity to exogenous hormonal interventions and high lability of functional state of the pituitary-ovarian system.

Effects of Stimulation and Blockade of D2 Dopamine Receptors on the Behavior of Gonadectomized Male Rats

The aim of the present work was to compare the effects of stimulation and blockade of D2 dopamine receptors on depression-like behavior in male rats in conditions of androgen deficiency. The D2 dopamine receptor agonist quinpirole (0.1 mg/kg, i.p.) and the D2 dopamine receptor antagonist sulpiride (10.0 mg/kg, i.p.) were given daily for 14 days both alone and in combination with low-dose testosterone propionate (0.5 mg/kg, s.c.) to gonadectomized (GE) males. Dopaminergic substances were given before behavioral testing and then throughout the test period. Depression-like behavior was assessed using the Porsolt test, while the nature of orientational-exploratory behavior was evaluated using the open field test. Chronic administration of sulpiride to GE males did not produce any significant change to the extent of depression-like behavior in the Porsolt test as compared with the control group (p > 0.05). However, combined administration of sulpiride and low-dose testosterone propionate to GE males led to a prodepressant effect as compared with controls (p < 0.05). In the open field test, this group of rats showed increases in grooming and exploratory activity from the levels seen in controls (p < 0.05). Use of quinpirole or its combination with low-dose testosterone propionate produced a marked antidepressant effect in the Porsolt test (p < 0.05) as compared with the control groups and GE males given testosterone propionate only. The combination of quinpirole and testosterone propionate produced positive effects which were the sum of the individual effects of the two substances alone on the level of depressivity in the Porsolt test. Administration of quinpirole alone or in combination with low-dose testosterone propionate did not alter total movement activity but increased the proportion of grooming in GE males from the control level. The results obtained here provide evidence that stimulation of D2 dopamine receptors leads to antidepressant actions in androgen-deficient male rats while blockade of D2 dopamine receptors, conversely, has a prodepressant effect.

Features of the Action of Combined Administration of NAN-190 and Ketanserin with Low-Dose 17β-Estradiol on Depression-Like Behavior in Prenatally Stressed Rats

The aim of the present work was to compare the effects of blockade of 5-HT1A or 5-HT2A/2C serotonin receptors on depression-like behavior in adult female rats with experimental estrogen deficiency whose mothers had been subjected to prenatal stress during pregnancy. Two weeks after removal of the ovaries, ovariectomized (OE) prenatally stressed female rats received chronic administration of the 5-HT1A serotonin receptor antagonist NAN-190 (0.1 mg/kg, i.p.) or the 5-HT2A/2C serotonin receptor antagonist ketanserin (0.1 mg/kg, i.p.) alone or in combination with a low dose of 17β-estradiol (0.5 μg/rat, s.c.) for 14 days before behavior tests started and then until tests were completed. The behavioral methods used were the Porsolt test and the open field test. The results showed that chronic administration of NAN-190 to OE prenatally stressed females led to a prodepressive effect, while the combination of NAN-190 with low-dose 17β-estradiol, conversely, had an antidepressant effect in the Porsolt test. In the open field test, these two experimental groups of rats showed decreases in the amounts of grooming reactions, vertical motor activity, and exploratory activity. Administration of ketanserin to OE prenatally stressed females produced an antidepressant effect, as compared with control animals. However, combined administration of ketanserin and low-dose 17β-estradiol to OE prenatally stressed females had no positive effect on the behavior of the animals in the Porsolt test.

Effects of an Agonist and an Antagonist of α4b2-n-Cholinoreceptors on Learning in Female Rats in the Main Phases of the Estral Cycle

The studies reported here provide a comparative analysis of the involvement of α4β2-n-cholinoreceptors in conditioned reflex activity in adult female rats during cyclic changes in sex hormone levels. The effects of chronic administration (14 days) of the α4β2-n-cholinoreceptor agonist RJR-2403 (1.0 mg/kg, i.p.) and the α4β2-n-cholinoreceptor antagonist mecamylamine (1.0 mg/kg, i.p.) on conditioned reflex activity were studied using models of spatial and nonspatial learning in female rats at different phases of the estral cycle. Nonspatial learning processes were evaluated using a conditioned passive avoidance reflex and spatial learning processes using the Morris water maze. Administration of RJR-2403 improved acquisition of the passive avoidance reflex in females in proestrus and estrus, as compared with control rats. Similarly, use of RJR-2403 restored the spatial learning ability of females in proestrus and had a stimulatory effect on the dynamics of spatial learning in estrus in the Morris water test. Conversely, chronic administration of mecamylamine impaired nonspatial and especially spatial learning in females independently of the phase of the estral cycle. The results obtained here provide evidence that stimulation of α4β2-n-cholinoreceptors has positive influences on conditioned reflex learning in female rats in different phases of the estral cycle.