[The effect of prenatal stress on antioxidant glutathion-assosiated enzymes activity in subcellular fractions of rat's liver]. / Vliianie prenatal'nogo stressa na aktivnost' glutation-zavisimykh antioksidantnykh fermentov v subkletochnykh fraktsiiakh pecheni krys.

The activity of glutathione-associated antioxidant enzymes in subcellular fractions (cytosolic, mitochondrial, and cell nucleus fractions) was investigated in the liver of adult male Wistar rats born after prenatal stress was. Two groups of animals were studied in the experiment: (1) control group included - animals was born by intact mothers, and (2) prenatal stress group included animals whose mothers were subjected to immobilization stress in high-light conditions from the 15th to the 19th day of pregnancy. The activity of glutathione peroxidase (EC 1.11.1.9) in prenatally stressed animals decreased in the fractions of nuclei and mitochondria compared to the control group, while the activity of glutathione reductase (EC 1.8.1.7.) increased in the same subcellular fractions. The activity of glutathione transferase (EC 2.5.1.18) in prenatally stressed rats reduced in the cytosol and mitochondrial fractions as compared to control group. Redistribution of the antioxidant enzyme activity in the cytosol, the fraction of nuclei and the mitochondrial fraction of liver tissue may contribute to the formation of the pathological phenotype of prenatally stressed offspring.

Selective effect of allopregnanolone on corticoliberin-induced anxiety.

We studied the effect of allopregnanolone on stress-induced anxiety caused by intranasal administration of corticoliberin to male Wistar rats. Active and passive rats were selected by their T-maze behavior and then were tested in elevated plus maze for initial anxiety level. Basing on test results, the animals were divided into following groups: active high-anxiety rats, active low-anxiety rats, and passive animals. Rats of the experimental subgroups received subcutaneous injection of allopregnanolone (0.2 mg/kg body weight), control animals received saline. In 30 min, all animals intranasally received corticoliberin (0.5 µg into each nostril) and then were tested in elevated plus maze. Passive animals demonstrated increased anxiety after corticoliberin administration against the background of allopregnanolone. Under the same conditions, low-anxiety rats demonstrated reduced anxiety, while in active high-anxiety animals, only an increase of motor activity was observed. Hence, the effect of allopregnanolone on anxiety level under stress conditions depends on individual typologic features of animal behavior.

[The effect of dehydroepiandrosterone-sulphate on stress behavior in high- and low-anxiety rats].

We studied the effect of preliminary three-fold administration of dehydroepiandrosterone-sulphate (DHEA-S) on behavioral disturbance, induced by water-immobilization stress in high- and low-anxiety active rats. Active rats were selected from Wistar rats on the basis of T-maze testing. Active rats were then divided into the groups with high and low anxiety level after testing in elevated plus maze. We found that DHEA-S injections (3 mg/100 g, i.p.) had an anti-stress-like effect, as shown by a decrease stress corticosterone level in both groups of rats. DHEA-S also demonstrated an anxiolytic-like effects in high anxiety rats and anxiogenic-like effects in low anxiety rats. These results suggest that DHEA-S anxiolytic and anti-stress effects depend on the individual psycho-emotional status and baseline anxiety level.

[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 corticoliberin on synaptic transmission in rat olfactory cortex slices in a water immersion model of depression.

Corticoliberin (corticotrophin-releasing factor, CRF, CRH) is an active regulator of endocrine, autonomic, and immune functions in stress, as well as a mediator of anxiety, determining the behavioral stress response. The present report describes studies of its action on neuron activity evoked by microstimulation of olfactory cortex slices. Behavioral testing in a T maze was used to select individuals with a passive behavioral strategy from a population of Wistar rats, and the animals were subjected to water immersion. Olfactory cortex slices were prepared 10 days later and evoked focal potentials were recorded on perfusion with medium containing corticoliberin (0.1 microM). Among active rats, 60% of slices retained high excitability after stress, and corticoliberin produced only insignificant reductions in the amplitudes of excitatory potentials in these slices, simultaneously increasing the amplitudes of inhibitory potentials. Low excitability was found in 40% of slices from active stressed rats, and corticoliberin had a significant inhibitory effect in these slices. Addition of corticoliberin to the incubation medium used for slices from passive rats with initially low excitability led to complete blockade of synaptic transmission. These data support the involvement of corticoliberin in the development of depression.

Effects of exogenous application of corticotropin-releasing hormone to slices of the olfactory cortex from rats with an active strategy of adaptive behavior on the water-immersion model of depression.

Experiments were performed on male Wistar rats. The specimens with an active strategy of behavior were exposed to unavoidable water-immersion stress. Surviving slices of the olfactory cortex were obtained 10 days after stress. The neurohormone had a strong inhibitory effect in 40% slices from active rats. The activity of glutamate receptors decreased, while the function of GABA receptors increased in 60% slices. Our results indicate that the depressive state of behaviorally active animals due to exposure to unavoidable stress is not necessarily mediated by the corticoliberinergic mechanisms in cortical structures.

Electrophysiological characteristics of depressive states in rats with passive strategies of adaptive behavior.

The behavior of rats in a T-maze was used to select individuals with a passive strategy of adaptive behavior from a population of Wistar rats. These animals were subjected to water immersion and olfactory cortex slices were prepared from the brain 10 days later and used for recording of evoked focal potentials and the effects of tetanic stimulation. Postsynaptic potentials, of both the AMPA and NMDA types, were initially of decreased amplitude in passive rats. After unavoidable stress, the suppression of excitatory potentials increased and there was a simultaneous increase in the amplitude of inhibitory GABAB-ergic mechanisms. Addition of corticoliberin (10(-10) M) to the incubation medium led to reversible blockade of synaptic transmission. Tetanic stimulation of slices from stressed rats led to the development of posttetanic depression in 84% of cases and to post-tetanic potentiation in 12%; this is evidence for profound changes in synaptic transmission. Thus, activation of corticoliberinergic mechanisms in cortical structures does not promote recovery from depressive states in rats with the passive behavioral strategy induced by unavoidable stress.

[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.

[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.

Blockade of corticoliberin receptors prevents the development of post-stress psychopathology in rats with an active strategy of adaptive behavior.

Active and passive Wistar rats were subjected to single water immersions, after which they showed signs of post-stress depression. Administration on this background of the peptide CRH-R1 receptor blocker astressin prevented the development of behavioral deficit in active individuals but had no effect on the behavior of passive rats. These results lead to the conclusion that corticoliberin receptor blockers are effective in the treatment of post-stress depression only for individuals with an initially active behavioral strategy.

Changes in the adaptive behavior of active and passive wistar rats in a water immersion model of depression.

Animals with active and passive strategies of adaptive behavior were selected from a population of Wistar rats by testing in a T maze to measure the indexes of behavioral passivity and behavioral activity. After single (stress) or two (stress-restress) water immersions, individual changes in adaptive behavior were used to study the development of post-stress psychopathology and its interaction with the initial behavioral strategy. In the unavoidable aversive environment, active and passive rats developed different types of post-stress depression, only passive individuals fulfilling the criteria of post-traumatic stress disorder.

[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.