[Selective influence of dehydroepiandrosterone-sulphate on anxiety induced by corticotropin-releasing hormone injection].

The objective of this study was to ascertain the effect of dehydroepiandrosterone-sulphate (DHEA-S) on changes of anxiety level, induced by corticotropin-releasing hormone (CRH) injection. Active and passive rats were selected from Wistar rats on the basis of T-maze testing. Active rats were then divided into the groups with high (HA) and low anxiety (LA) level after testing in elevated-plus maze. Intranasal injection of CRH induced increase of anxiety level in the LA rats, while in HA rats it remained unchanged. DHEA-S exerted a moderate anxiolytic effect on the LA rats and sedative effect--on the HA rats. DHEA-S injection had no effect on anxiety level in passive rats that typically demonstrate high level of trait-anxiety and resistance to CRH. These results suggest that DHEA-S effect depends on the individual psycho-emotional status and responsiveness to CRH.

[Effects of the corticoliberin on synaptic transmission in the rat olfactory cortex slices in water-immersion model depression].

Corticoliberin (corticotrophin-releasing hormone, CRH) regulated of endocrine, autonomic and immune response to stress and is a mediator of anxiety in behavioral response. We studied the effect of corticoliberin on neuronal activity after microstimulation of olfactory cortex slices. Wistar rats strain were selected in T-maze labyrinth according to active and passive strategy of the adaptive behavior. The rats were exposed to water-immersions stress and after 10 days from their brain the olfactory cortex slices were prepared. The evoked focal potential were registered after perfusion with 0.1 mcM of CRH. It was revealed that in 60% of the slices of the active rats CRH induced the small decrease of excitatory amplitude but the increase amplitude inhibitory postsynaptic potential. In 40%, CRH induced the depression of synaptic transmission. Addition of CRH in incubation medium of the passive rat slices related, blockade the synaptic transmission.

[Peroxidation of lipids in the brain of active and passive rats during development of poststress depressions].

Peroxidation of lipids in a cortex of the large hemispheres, striatum, hippocampus and hypothalamus of rats of the lina KHA and KLA (Koltushi High and Low Avoidance) during development of poststress depressions was studied. After emotional painful act in initial terms of change, peroxidation of lipids had phasic character and differed in precise structural specificity. During maximal development of depression, the most expressed infringements of lipids peroxidation occurred in KHA rats in striatum and hippocampus, and at KLA rats--in the striatum and hypothalamus. The data confirm the important role of initial strategy of behavioral in mechanisms of pathogenesis of poststress psychopathology.

[Electrophysiological characteristics of depressive conditions with passive strategy of the adaptive behavior in rats].

Wistar rats strain with passive strategy of the adaptive behavior were selected in T-maze labyrinth. The rats were exposed to water-immerssions stress and after 10 days from their brain the olfactory cortex slices were prepared. The evoked focal potentials were registered in slices. It is shown that the amplitudes of the AMPA and NMDA EPSPs were reduced as compared to control (rats without stress). The amplitude of the GABABergic inhibitory postsynaptic potentiation was increased after stress. Additions of the corticotropin-releasing hormone (10(-10) M) in incubation medium result in reversible inhibition of synaptic transmission. Tetanic stimulation of the slices induced of the long-term posttetanic depression in 84 % slices and in 12 %--to the long-term posttetanic potentiation. It is indicates that the significant disturbances in synaptic transmission in slices. Thus the activation of the corticotrophinergic mechanisms in cortical structures not promots the removal of the rats depressive state with passive strategy of the adaptive behavior induced by inescapable stress.

[Corticosteroid hormones in pathogenetic heterogenety of post-stress depression].

The role of corticosteroid hormones in post-stress depression progress and their usage for correction of this psychopathology was studied in active and passive Wistar rats. It was found that only passive individuals had sensitivity to corticosteroids and, among them, only adrenal gland hormones lead to corrections of post-stress depression.

[Alteration of active and passive Wistar rats adaptive behavior in water-immersion model of depression].

Animals with active and passive behavioral strategy were selected among male Wistar rats by testing them in the T-maze. Using the results of rats testing in T-maze index of behavioral activity and index of behavioral passivity were calculated. The development of post-stress psychopathology and ils correlation with initial behavioral strategy were studied under water-immersion stress conditions consiclering individual alteration of adaptive behavior. Two paradigms were used--one time trial (stress) and two times trial (stress-restress). It was found that active and passive rats being subjected to inescapable aversive exposure develop different types of post-stress depression and only passive animals show the signs of posttraumatic stress disorder.

[Hormonal function of the hypophyseal-adrenocortical system in the pathogenetic heterogeneity of post-stress depressions].

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.

[Psychomotor responsiveness to corticoliberin in rats with active and passive adaptive strategy in water-immersion paradigm of depression].

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.

[Blockade of corticoliberin receptors prevents development of poststressor psychopathology in rats with active strategy of adaptive behaviour].

Active as well as passive Wistar rats were subjected to a single water-immersion action that gave rise signs of poststressor depression in them. Administration of CRH-R1-receptor peptide blocker astressin prevented development of behavioural deficiency in active rats and did not affect behaviour of passive rats. This suggests that the corticoliberin receptor blockers are only effective for treatment of poststressor depressions in individuals with initially behavioural strategy.

[Morpho-functional alterations of the adrenal cortex in rats with active and passive strategy of adaptive behavior].

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.

[The role of corticotropin-releasing hormone in alteration of adaptive behavior of the active and passive rats after inescapable stress].

Effects of corticotropin-releasing hormone (CRH) on the formation of post-stress psychopathology were studied using of two genetic strains KHA (Koltushi high Avoidance) and KLA (Koltushi low Avoidance) selected on high or low acquisition of active avoidance, respectively. These strains are characterized by higher (KHA) and lower (KLA) behavioral activity in open field and adopted, respectively, active and passive strategies in stressful conditions. A widely used experimental paradigm of learned helplessness where behavioral depression was produced by inescapable uncontrollable footshock has been applied in our study. KHA rats demonstrated psychopathology already 1st day following exsposure to the stress faktor, and the depression progressed by the 5th and 10th post-stress days. Intranasal application of CRH facilitated the development of depression in active rats. In KLA rats, which originally displayed low exploratory activity associated with high anxiety, the inescapable stress at first enhanced the exploratory behavior but 10 days later these rats displayed a progressive decline of exploration and locomotion. Initially, the application of CRH also enhanced the exploratory behavior in these rats, but to 10th post-stress day promoted development of depressive state. The results suggest that CRH in different ways affects the formation of depressive state in rats with different strategies of adaptive behavior.

[Dynamics of hypothalamic CRH immune reactivity in active and passive rats in the course of development of behavioural depression]. / Soderzhanie kortikoliberina v gipotalamuse krys s razlichnoi strategiei povedeniia pri poststressornoi depressii.

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.

[Corticotropin-releasing hormone in the regulation of adaptive behavior]. / Kortikotropin-rilizing gormon v integratsii éndokrinnykh funktsii i povedeniia.

Recent findings on the role of corticotropin-releasing hormone (CRH) in the regulation of stress and its consequences are summarized and analyzed in the review. Being involved in stress-activating system this neurohormone is referred to as a neurochemical factor triggering and integrating both endocrine and behavioral functions. The CRH distribution in hypothalamus and extrahypothalamic brain regions relevant to its involvement in the controlling of endocrine processes and behavior is viewed in details. Distinct behavioral outcomes of stress and the contribution of amygdalar, hippocampal, and striatal CRH-structures, implicated in general organism response to external influences, are widely discussed. From this viewpoint the mechanisms involved in the development of post-stress psychopathology, as well as drug addiction and alcoholism are treated.

[Stress responsiveness of the hypophyseal-adrenocortical system in rats with active and passive types of behaviour]. / Reaktivnost' gipofizarno-adrenokortikal'noi sistemy na stress u krys s aktivnoi i passivnoi strategiiami povedeniia.

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.

[Adaptive behavior of active and passive rats after intranasal administration of the corticotropin-releasing hormone]. / Prisposobitel'noe povedenie aktivnykh i passivnykh krys posle intranazal'nogo vvedeniia kortikotropin-rilizing gormona.

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.

[Corticoliberin protects the olfactory cortex slices against the negative effect of "dysfunctins"]. / Kortikoliberin protektiruet neirony perezhivaiushchikh srezov oboniatel'noi kory ot negativnogo vliianiia "disfunktsinov".

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.

[Dopaminergic processes in the striatum mediating corticoliberin effect on behavior of active and passive rats]. / Uchastie dofaminergicheskikh protsessov v striatume v deistvii kortikoliberina na povedenie aktivnykh i passivnykh krys.

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.

[Individual typological characteristics of hormonal responses in dogs during psychoemotional stress]. / Individual'no-tipologicheskie osobennosti gormonal'nykh reaktsii u sobak pri psikhoémotsional'nom stresse.

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.

[Early gene expression in the rat brain following administration of corticoliberin in the neostriatum]. / Ekspressiia rannikh genov v mozgu krys posle vvedeniia kortikoliberina v neostriatum.

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.