V. V. Rakitskaya

Neuroendocrine mechanisms of the formation of adaptive behavior.

The behavioral and neuroendocrine responses of the body to external changes are determined by genetically determined programs of individual development, and are established during pre- and post-natal ontogenesis. These responses, however, can be changed by stress or administration of corticosteroid hormones in “critical periods” of the bodys development. Mineralo- and glucocorticoid receptors mediate the “inhibition” of particular neuroendocrine or neuromediator systems, promoting behavioral modification.

Involvement of the striatum in the central regulation of the hormonal functions of the gonads.

Studies reported here show that intrastriatal administration of corticoliberin to rats decreases the blood testosterone level. However, in conditions of chemical deficiency of dopaminergic transmission in the dorsal striatum induced by injection of 6-hydroxydopamine, the effect of this neurohormone did not appear. It is concluded that extrahypothalamic corticoliberin is involved in regulating the hormonal reproductive system acting via dopaminergic mechanisms.

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.

Lipid Peroxidation in the Striatum of Rats during Stress after Administration of Cortisol

Lipid peroxidation processes were studied in the striatum during stress in conditions of prior administration of cortisol. Three doses of cortisol (25 mg/kg, daily) had no significant effect on the levels of lipid peroxidation products six days after injections ended. However, lipid peroxidation responses to stress during this period in animals given cortisol were significantly stronger than in controls (there were decreases in the intermediate products of lipid peroxidation and increases in the quantities of Schiff bases). Thus, administration of hormone leads to long-term changes in one of the most important regulatory systems of the body – lipid peroxidation – and has sensitizing effects on changes in the levels of stress-induced lipid peroxidation products.

Involvement of Dopaminergic Processes in the Striatum during the Effects of Corticoliberin on the Behavior of Active and Passive Rats

The effects of intranasal corticoliberin on behavior in the open field test were studied in rats with active and passive behavioral strategies (lines KHA and KLA); levels of dopamine and noradrenaline and their metabolites were measured in the striatum and hypothalamus. In KLA rats, administration of the neurohormone led to increases in motor and investigative activity, while decreases were seen in KHA rats. There were no interline differences in catecholamine levels in the hypothalamus, while dopamine levels in the KLA striatum nearly doubled and metabolite levels (DOPAC, HVA) were significantly lower than in KHA rats. Corticoliberin increased dopamine and noradrenaline levels in the hypothalamus of both rat lines, with significant decreases in the striatum. This decrease was more marked in KLA rats, probably due to the faster metabolism of transmitters in the presence of neurohormones, as indicated by the increase in metabolite levels in this structure.

Development of Behavioral and Hormonal Disorders in Prenatally Stressed Female Rats on the Model of Posttraumatic Stress Disorder

The dynamics of changes in behavioral and hormonal manifestations of a pathological state in mature female rats born by mothers exposed to daily restraint stress on days 15-19 of pregnancy were studied in the experimental model of posttraumatic stress disorder (stress–restress paradigm). Experiments demonstrated increased anxiety in control and prenatally stressed female rats after combined stress followed by restress. This parameter remained enhanced until day 10 after restress in control rats and day 30 in prenatally stressed animals. The severity of depression increased on days 1 and 10 after restress in prenatally stressed female rats. Basal activity of the pituitary–adrenocortical axis increased only in prenatally stressed female rats under these conditions. This parameter increased 1 day after restress and decreased after day 30. It was concluded that prenatal stress could increase the predisposition to post-stress mental pathologies in experimental animals, which are manifested in increased severity and duration of behavioral and hormonal impairments.

Expression of vasopressin in the hypothalamus of active and passive rats with poststress depression.

No interstrain differences were revealed in vasopressin concentration in the hypothalamus of control and treated active and passive rats with poststress depression. Changes in vasopressin immunoreactivity corresponded to variations in corticotropin-releasing hormone concentration observed in this model of depression. These data suggest that vasopressin contributes to the development of this experimental psychopathology.

Functioning of hypophysial adrenocortical system in rats selected by the threshold of sensitivity to electrical current

An enhancement of stress reactivity of the hypophysial-adrenocortical system in response to emotional and physical influence was shown in rats with a low threshold of sensitivity to electrical current. This phenomenon was observed as a rise in the maximum level of blood corticosterone and acceleration of stressor hormonal response. In the high-threshold rats a decrease in sensitivity of the hypophysial adrenocortical system to the feedback signals was observed.

Stress-Induced Changes in Corticoliberin and Vasopressin Expression in the Hypothalamus of Female Rats in a Model of Post-Traumatic Stress Disorder

We report here our studies of the neuroendocrine mechanisms underlying the development of an anxiety-like state in female rats at different phases of the estrous cycle (blood estradiol level) in a stress–restress post-traumatic stress disorder (PTSD) model. Quantitative immunocytochemical methods were used to demonstrate an increase in corticoliberin expression in the paraventricular nucleus (PVN) of the hypothalamus in female rats 10 days after restress in all experimental groups. On post-restress day 30, the level of corticoliberin expression in the PVN of the hypothalamus decreased to the level seen in the control group. A significant increase in vasopressin immunoreactivity during development of the anxiety-like state was seen only in the PVN of the hypothalamus in female rats in the estrus phase (low estradiol level) at the moment of severe combined stress in the stress–restress model. Thus, the most significant changes in the neuroendocrine system of the hypothalamus was seen in female rats subjected to stress in the estrus phase, this consisting of a sharp decrease in the endogenous plasma estradiol level. Hyperactivity of the hypothalamic component of the vasopressinergic system can evidently be regarded as one of the mechanisms forming the experimental anxious PTSD-like state in female rats in the stress–restress model.

Activity of the Hypothalamo-Hypophyseal-Adrenocortical System in Prenatally Stressed Female Rats in a Model of Post-Traumatic Stress Disorder

Changes in the activity of the hypothalamo-hypophyseal-adrenocortical system (HHAS) were studied in adult prenatally stressed female rats in an experimental model of post-traumatic stress disorder (PTSD) in which the animals were subjected to combined treatment consisting of restraint for 2 h, swimming for 20 min, and ether stress, with subsequent restress seven days later (the stress–restress paradigm). An increase in the HHAS stress response was seen after combined stress in prenatally stressed females, apparent at the time of restress. Both control and prenatally stressed animals showed increases in the sensitivity of the hormonal axis to negative feedback signals, which supported accelerated inhibition of the HHAS after its activation by stress. Only prenatally stressed females showed a decrease in the basal corticosterone level and persistence of increased HHAS sensitivity to feedback signals one month after stress and restress. Control females were found to form the PTSD-like state after stress–restress mainly via corticotropin-releasing hormone, while vasopressin was involved in this process in prenatally stressed females.