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.

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.

Free-radical lipid oxidation in the brains of active and passive rats during the development of post-stress depression.

Free-radical lipid oxidation was studied in the cerebral cortex, striatum, hippocampus, and hypothalamus of KHA and KLA rats (Koltushi High and Low Avoidance) during the development of post-stress depression. After unavoidable emotional-pain exposure, changes in the free-radical oxidation of lipids were phasic in nature and had a clear structural specificity in the early phases. During the maximum development of depression, the most marked impairments to lipid peroxidation were seen in KHA rats in the striatum and hippocampus, while the greatest changes in KLA rats were seen in the striatum and hypothalamus.

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.

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.

Reactivity of the hypophyseal-adrenocortical system to stress in rats with active and passive behavioral strategies.

Rats with active (KHA) and passive (KLA) behavioral strategies showed no strain-related differences in basal corticosterone levels or in changes in corticosterone levels after exposure to mildly stressful stimuli. Only severe immobilization stress produced significant interstrain differences in the reactivity of the hypophyseal-adrenocortical system, as evidenced by the greater increase in blood corticosterone in KHA rats 30 min after stressing. The hormonal stress response in KHA rats was prolonged, as the elevated blood corticosterone level in these animals persisted longer than in KLA rats.

Adaptive behavior in active and passive rats after intranasal administration of corticotrophin-releasing hormone.

Rats with high (KHA) and low (KLA) rates of acquiring active avoidance reflexes were used to study the effects of intranasal administration of corticotrophin-releasing hormone on orientational-investigative behavior in an open field and anxiety in an elevated cross maze. Administration of the neurohormone induced opposite changes in the behavior of the rats of these lines in the two tests. In KLA rats, movement and investigative activity increased, while in KHA rats these behaviors decreased.

Neurophysiological effects of corticotropin-releasing factor in living slices of the olfactory area of the rat cortex.

Application of corticotropin-releasing factor (CRF) at concentrations of 10(-9) and 10(-8) M to living brain slices induced activation of the pre- and postsynaptic excitatory components of focal potentials recorded in the slices. The amplitudes and durations of the AMPA and NMDA components of EPSP increased during exposure to CRF, while the amplitude of the GABA(B)-mediated IPSP was suppressed. At the higher CRF concentration (10(-8) M), cells in slices showed epileptiform discharges.

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 protects neurons from the negative influences of "dysfunctins" in living olfactory cortex slices.

The protective effects of corticoliberin on living rat olfactory cortex slices during perfusion with "dysfunctins" extracted from cerebrospinal fluid of drug addicts were studied. Isolated perfusion of slices with medium containing "dysfunctins" led to irreversible suppression of the amplitude of individual components of focal potentials induced by electrical stimulation of the lateral olfactory tract. The maximum level of depression was seen for the AMPA and NMDA components of EPSP.

The role of sex steroids in forming anxiety states in female mice.

Natural fluctuations in sex hormones during the ovarian cycle have enormous influences on ongoing psychological status in the female body. We report here studies of the effects of exogenous sex steroids on anxiety levels in female mice, as evaluated in the elevated cross maze test. Female NMRI mice were subjected to bilateral oophorectomy and one week later received s.

Localization of corticoliberin receptors in the rat brain.

In situ hybridization was used to study the distribution of corticoliberin receptors of subtypes 1 and 2 (CL-R1 and CL-R2 respectively) in different structures of the rat brain. Levels of CL-R1 mRNA in the brain were significantly greater than levels of CL-R2 mRNA, and the most intense expression of the CL-R1 gene was seen in forebrain structures, especially various neocortical, archicortical, and paleocortical regions in the cerebellar cortex. In addition, significant levels of CL-R1 mRNA expression were noted in the red nucleus and the reticular nucleus of the tegmentum.

Expression of early genes in the rat brain after administration of corticoliberin into the neostriatum.

In situ hybridization using oligonucleotide probes was used to study the effects of intrastriatal microinjection of corticoliberin on the expression of the early genes c-fos, jun B, c-jun, and NGFIA in the rat brain. Administration of corticoliberin (0.25 microg) into the neostriatum induced the expression of mRNA encoded by the early genes c-fos, jun B, and NGFIA in both the neostriatum itself and in its efferent structures, particularly the nucleus accumbens and various parts of the cortex.

The neonatal glucocorticoid treatment-produced long-term changes of the pituitary-adrenal function and brain corticosteroid receptors in rats.

Two distinct periods of sensitivity to elevated glucocorticoid hormone levels during postnatal development of the pituitary-adrenal axis were studied. Wistar rats were injected subcutaneously (s.c.

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.

Dopaminergic mechanisms of neostriatum in the regulation of adaptive behavior by corticoliberin.

A conditioned active avoidance response was developed in rats with high (KHA) and low (KLA) rates of learning and the effects of injection of corticoliberin into the dorsal striatum on orientational-investigative and avoidance behavior were studied in normal animals and after depletion of striatal dopamine by preliminary injection of 6-hydroxydopamine. These studies showed that corticoliberin, like 6-hydroxydopamine, produced similar trends in the animals' behavior. Their effects were mediated by opposite mechanisms in animals with initial active and passive learning strategies for adaptive behavior.

Striatal mechanism of action of corticoliberin on behavior in dogs in conditions of dopamine deficiency.

This report describes studies of the interaction of the integrative dopaminergic and corticoliberin systems in the neostriatum during performance of situational food-related conditioned reflexes. Studies were performed in dogs with chemotrodes implanted in the substantia nigra and the head of the caudate nucleus. 6-Hydroxydopamine was injected into the substantia nigra at a dose of 50 microg, and 10 microg of corticoliberin was injected into the caudate nucleus.

Modification of the behavioral effects of corticoliberin by early post-natal administration of corticosteroid hormones.

Experiments on rats in which hydrocortisone was given in the early postnatal period were used to study the effects of intrastriatal microinjection of corticoliberin on behavior in an open field test. Bilateral microinjection of corticoliberin into the neostriatum led to a sharp reduction in orientational-investigative activity. Rats given hydrocortisone in the first days of life had elevated movement activity, and the anxiogenic effect of corticoliberin was absent in these animals.

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 body's development. Mineralo- and glucocorticoid receptors mediate the "inhibition" of particular neuroendocrine or neuromediator systems, promoting behavioral modification.

Receptor binding of corticosterone in some rat brain structures following neonatal blockade of the hypophyseoadrenal system.

Administration of hydrocortisone to rats during the first five postnatal days leads to the blockade of the hypophyseoadrenal system and results in a decrease in the number of corticosterone receptors in the hypophysis, hypothalamus, and hippocampus. Such a decrease in the receptor binding of corticosterone in the brain structures involved in the regulation of the hypophyseoadrenal system by a feedback mechanism is due to a change in the number of true glucocorticoid receptors.