Biomedical subjects
Publications and source records attributed to V G Shaliapina.
Original behavioral strategy is an important prerequisite for the pathogenesis of post-stress psychopathologies. Heterogeneity of these pathologies depends on the functional activity of hypophyseal-adrenocortical system.
A single intranasal injection of CRH alters adaptive behavior only in active rats. In particular this procedure results in increase of their behavioral passivity and reduction of psychomotor responsiveness. This neurohormone causes the same effect in active rats being injected by means of the same routine 20 days after animals have been exposed to a single water-immersion stress. But this effect of CHR is not observed after injection of the neurohormone to depressed animals in the stress-restress paradigm. Passive rats, intact or depressed, do not show any behavioral changes, while active ones develop signs of depression after repeated CRH intranasal injection.
In rats with the active (KHA strain) and passive (KLA strain) coping strategies, a post-stress depression develops respectfully on the 1st or 10th day after the inescapable stress. The present study revealed an increase of adrenal weight and blood corticosterone levels on a day following the inescapable stress, as well as marked fluctuations of blood glucose in one and five days post-stress in KHA rats. By the 10th day, these indices returned their basal levels. In contrast, the stress reactivity of KLA rats was lower in all terms and their corticosterone levels remained reduced on the 10th day after stress. In KLA rats, the fasciculate zone was reduced but reticulated zone grew in Ith day following the stress, while in KHA rats the inescapable stress resulted in growth fasciculate zone and concomitant reduction of reticulate zone, both evident on the 10th post-stress day. The data indicate that the development of post-stress depression in KLA rats is probably associated with exhaustion of adrenocortical function.
A possible relation between activity of the main CRH-producing centers of hypothalamus and depressive-like behavior of animals was studied. We used genetically selected strains--KHA (Koltushi High Avoidance) and KLA (Koltushi Low Avoidance) rats, demonstrating active and passive strategy of adaptive behavior in novelty situaltions, respectively. Rats were exposed to inescapable stress to develop a "learned helplessness". We observed considerable differences between two strains of animals in CRH-expression in parvo-, magno-cellular parts of the paraventricular nucleus and in the supraoptic nucleus in the course of behavioral depression development. Significant differences between control groups were seen only in paraventricular nucleus. On the 1st post-stress day in hypothalamus of KLA rats, we detected decreased CRH immune reactivity that remained unchanged up to the 10th day. In KHA rats, there were no notable changes of CRH expression in all studied nuclei. These findings, including previous results on different dynamics of behavioral changes and different hypothalamo-pituitary-adrenocortical system activity during development of depression in KLA and KHA rats, indicate that "learned helplessness" in these two groups of animals provides the model analogues of different types of depression. Besides, these findings indicate different implication of hypothalamus CRH-system in the behavioral depression development in rats with divergent strategy of adaptive behavior.
No linear differences in the corticosterone basal levels or in its changes following weak stress effects were revealed in rats with active (KHA) or passive (KLA) behavioural strategy. A strong immobilisation stress alone was able to evoke significant linear differences in the hypophyseal-adrenocortical system's responsiveness. The hormonal response to stress was prolonged in the KHA rats as the increased level of corticosterone in the blood of these animals was longer preserved than in the KLA rats. The results suggest both a different sensitivity of the hypophyseal-adrenocortical system and a different velocity of the stress response deactivation in active and in passive animals.
The action of intranasal corticotropin-releasing hormone (CRH) administration on open field behavior and striatal and hypothalamic levels of dopamine, noradrenaline and their metabolites has been studied in rats with different behavior strategies (KHA and KLA strains). In KLA rats, CRH administration resulted in increased locomotor and exploratory activity, while KHA rats demonstrated decreased that. The analysis of catecholamine levels did not detect any strain differences in hypothalamus, but in striatum the dopamine levels have been twice higher, while the metabolite levels (DOPAC and HVA) were significantly lower in KLA rats as compared to KHA rats. The CRH administration led to increased dopamine and noradrenaline levels in hypothalamus and decreased those in striatum in rats of both strains, but in KLA the decrease was more evident. It is probably a result of intensified mediator turnover induced by the neurohormone in KLA rats, as supported by a fact of increased dopamine metabolite levels in this structure.
Corticoliberin may induce protective effects via its specific receptors or unspecifically by means of the glutamate receptors. A combined action of these mechanisms is also possible.
Behavioural effect of intranasal application of corticotropin-releasing hormone (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked the opposed changes in behaviour of rats of this strain in both tests. The level of locomotion and exploratory activity rose in KLA rats and decreased in KHA rats. After the CRH application, the KLA rats but not KHA rats spent more time in the opened alleys of the PM than the control animals. The same behavioural changes were observed in our previous research when CRH was injected in striatum. We suppose that CRH is an endogenous factor of precise correction of the adaptive behaviour.
Using in situ hybridisation with oligonucleotide probes, an expression of immediate early genes c-fos, jun B, c-jun, and NGFIA in the rat brain was studied following intrastriatal microinjection of corticotropin-releasing hormone (CRH). The hormone induced expression of c-fos, jun B, and NGFIA mRNAs in the neostriatum as well as in its target brain areas, including nucleus accumbens and different cortical areas. The expression of c-jun mRNAs was unaffected. The findings indicate that neuronal activation of the neostriatum and its target brain areas provides one possible mechanism for mediating adaptive CRH actions in stress.
Effects of psycho-emotional stress on contents of steroid hormones in the blood were studied in dogs with different typological properties of the higher nervous activity. Under stress condition, a significant correlation between the cortisol and testosterone levels and the dogs' typological characteristics was found. The more obvious fluctuations in the hormones level occurred in animals with strong and excitable type of the nervous system as compared with dogs belonging to weak and inert type.
Female rats were subjected from the 14th to 17th day of pregnancy to immobilisation under conditions of 1-hour daily bright illumination. On the 20th day, contents of testosterone and estradiol was decreased with no sex difference in their level in the pregnant female rats' blood and in the amniotic fluid. Sex differences were flattened in 1-month litter both in the androgen and oestrogen contents and in adaptive behaviour. In prenatally stressed males, motor activity was inhibited and anxiety was enhanced as compared with the control. At one and a half months of age, the consequences of the prenatal stress disappeared and then reappeared after sexual maturation but with an opposite trend. Adaptive behaviour of adult males was less flexible and revealed no age-dependent oscillations inherent in the control animals. Prenatal stress while preventing the maximal raise of sex steroids in the blood shifts sex differentiation of the adaptive behaviour toward demasculinization.
Using the in situ hybridization, a distribution of corticotropin-releasing hormone (CRH) receptors CRH-1 and CRH-2 in the rat brain has been studied. Brain levels of CRH-1 mRNA were higher than the those of CRH-2 mRNA. Most intensive CRH-1 gene expression was observed in the forebrain, including neocortex, archicortex, paleocortex and cerebellar cortex. In addition, significant CRH-1 mRNA expression was detected in the red nucleus, pontine nucleus, cochlear nucleus and reticular tegmental nucleus. CRH-2 mRNA was intensively expressed in the olfactory structures, corticomedial amygdala, CA1-CA4 of hippocampus, ventramedial hypothalamus and several modullar nuclei. Moderate CRH-2 mRNA level were seen in the dorsomedial neostriatum. The findings indicate that within the brain two types of CRH receptors are widely expressed. A distinct pattern of CRH-1 and CRH-2 expression in the brain appears to underline the functional specifics of the CRH actions in brain structures.
Level of sex steroid hormones being changed throughout an estrous cycle influences physiological and behavioral features of female subjects. To test how estrogen and progesterone affect the anxiety level in mice the ovariectomy (OVX) followed by hormone treatment was carried out. After 1 week of recovery period estradiol benzonate (20 micrograms, s/c) was injected once a day during 7 consequent days. By the 7th day in addition to EB injection progesterone (500 micrograms, s/c) was also injected. Four hours later the mice were tested in elevated plus-maze to measure the anxiety level. Control animals were treated with sesame oil only. Behavioral data obtained demonstrate that the hormonal treatment altered anxiety state in experimental animals. In plusmaze paradigm, it has been demonstrated that progesterone-treated mice revealed the lowest level of open arm activity. In contrast, these mice showed the highest grooming activity as compared to other experimental groups. Immunohistochemical data on progesterone receptor (PR), immunoreactivity in brain have shown that the manipulation with different hormonal treatments modified the number of PR-ir cells in many brain areas. Our data suggest that sex steroid hormones play an important role in induction of anxiety level, as measured by elevated plus-maze, and this action might be partially mediated through the classical steroid receptors.
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Neostriatum and its dopaminergic mechanisms were shown to be involved in mediation of some adaptive effects of the CRH (corticotropin-releasing hormone), both behavioural and endocrine. The data obtained suggest that neostriatum contributes to a coping response by selecting an appropriate behavioural strategy in stressful situation.
Administration of cortisol on the 13th, 15th, and 17th days of postnatal ontogenesis was shown to exert a long-lasting modifying effect upon the hypophysis-adrenal system's (HAS) stress reactivity in the rat litter. The effect involved a longer duration of hormonal response to immobilisation stress: a longer-lasting elevation of the corticosterone level in the blood plasma suggesting a diminished sensitivity of the HAS to feed-back signal. In hippocampus, frontal cortex and hypothalamus of the experimental rats, a decrease in receptor binding of labeled corticosterone was revealed.
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