Open field behavior and the state of the thymus and adrenal glands in rats after exposure to stress and elevation of blood level of autoantibodies to dopamine and glutamate.

Blood level of autoantibodies to dopamine and glutamate in rats increased in 4 weeks after exposure to stress. Under these conditions, active animals demonstrated decreased motor and exploratory activity in the open field, while in passive animals, only the number of explored objects decreased. The increase in blood level of autoantibodies to dopamine and glutamate in rats exposed to stress was followed by an increase in the adrenal gland weight in active animals and thymus weight in passive animals. The increased blood level of autoantibodies to dopamine and glutamate in rats exposed to stress reflects the development of the long-term stress-induced response.

Increased ß-endorphin level in blood plasma as an indicator of positive response to depression treatment.

Preliminary data indicate that increased blood plasma level of ß-endorphin in patients with nonpsychotic unipolar depression after 2 weeks of treatment correlates with the positive response to therapy. This parameter can be regarded as an objective indicator of potential improvements. Further studies aimed at determining the value of blood ß-endorphin levels in patients with mood disorders for the diagnostics and estimating the therapeutic success in this disease are required.

[Central and peripheral mu-opioid systems in the mechanisms of emotional stress].

The aim of the work was to study effect of peripheral administration of mu-opioid receptor ligands unable to penetrate through the hematoencephalic barrier on the measures of emotionality in rats and on the release of beta-endorphins from nerve endings of the anterior cingulate cortex during emotional stress. The mu-opioid receptor agonist loperimide mostly acted as an anxiolytic whereas the receptor antagonist methylnaloxon showed depressive activity. Lifetime microdialysis and subsequent immunoenzyme assay demonstrated that intraventricular infusion of loperamide and methylnaloxon decreased and increased respectively the surge of beta-endorphin into the intercellular space. Immobilization-induced emotional stress insignificantly increased the beta-endorphin level in the cingulate cortex. Peripheral administration of loperamide but not methylnaloxon markedly increased the release of the neuropeptide during stress. These findings confirm the hypothesis of the authors about reciprocal interaction of central and peripheral components of the endogenous opioid system and explain the mechanism of antistress action of loperamide.

[Immune links in the system organization of behaviour].

The work is devoted to the research of immune mechanisms in self-control of various functional systems of homeostatic and behavioral levels. Distinction of immune mechanisms in rats with different prognostic stress-resistance is established. Immunization of rats by conjugates of various neuromediators with bovine serum albumin selectively changes the animals stress-resistance. Participation cytokines in reactions of a brain's separate neurons and their interaction with a leading neuromediator - norepinephrine is established. Individual changes of pro- and anti-inflammatory cytokines in blood serum are shown in rats with different stress-resistance. There are revealed features of morphological distinctions of immunogenic structures small intestine fabrics in animals with various behavioral activity in the "Open field" test.

[Influence of exposure to immobilisation stress on blood concentration of TNF alpha and IL-4 in rats active and passive in the open field test].

The influence of exposure to immobilization stress on TNF alpha and IL-4 concentrations in blood was studied in behaviorally active vs. passive in the open field Wistar rats. One hour after exposure to stress, blood concentrations of TNF alpha and IL-4 were significantly lower in behaviorally passive as compared to active rats and passive controls not exposed to stress. Moreover, in passive rats exposed to stress, the pituitary weight increased as compared to passive controls. Behaviorally passive rats exposed to emotional stress were characterized by a decreased blood levels of TNF alpha and IL-4 as compared to behaviorally passive controls and behaviorally active animals exposed to stress.

Involvement of autoantibodies to neurotransmitters in mechanisms of stress reaction in rats.

Combined stress exposure of rats can lead to the formation of autoantibodies to neurotransmitters. Repeated stress is associated with the production of autoantibodies to serotonin, dopamine, norepinephrine, glutamate, and GABA. High emotional and behavioral reaction to stress is associated with intensive production of autoantibodies to serotonin, dopamine, norepinephrine, and glutamate.

[Serotonin in brain regions of rats differing in their inborn locomotor activity]. / Soderzhanie serotonina v strukturakh golovnogo mozga u krys s vrozhdennymi razlichiiami v dvigatel'noi aktivnosti.

Serotonin contents in the paraventricular hypothalamic nucleus (PVN) and dorsal hippocampus of rats with different levels of inborn motor activity were studied by microdialysis in basal and stimulated conditions. Rats were exposed to elevated platform and forced swimming stress. In basal conditions, differences in serotonin contents between rats with different levels of inborn motor activity were found neither in hippocampus nor in PVN. In both kinds of stress conditions, serotonin content in hippocampus increased only in rats with higher level of inborn motor activity. Serotonin content in PVN dramatically increased during forced swimming in both rat groups. This increase was significantly more pronounced in rats with low activity. The data suggest that serotonin release in stress depends on inborn motor activity, brain area dialyzed, and the stressor the animals were exposed to.

Genetic predisposition to anxiety-related behavior predicts predator odor response.

While rodents have a keen sense of smell and largely depend on olfactory cues for operating in their environment, most of the widely used tests to assess anxiety-related behavior largely ignore the olfactory system, being primarily based on fear of brightly lit, novel and open spaces. Here, we aimed at testing whether the genetic predisposition to anxiety predicts the predator odor response in mice. In the first experiment, using the 3-chamber avoidance test in CD-1 mice, trimethylthiazoline (TMT), a synthetic fox fecal odor, was shown to induce stronger behavioral and neuroendocrine effects than cat odor and butyric acid, respectively, and was therefore chosen as aversive odor for the following series of experiments. In this series, bidirectionally, selectively inbred CD-1 mice with either high (HAB), intermediate (NAB) or low (LAB) anxiety-related behavior responded differently to TMT, with HABs spending significantly less time than both NABs and LABs in the chamber harbouring the predator odor. Importantly, this result is not confounded by any deficit of the olfactory system, as LAB and NAB mice, while not or only moderately responding to TMT, responded to both the pleasant odor of female urine and the repugnant odor of butyric acid. Probably due to the strength of TMT, a similar increase in corticosterone levels upon predator odor exposure was observed in all three groups. Together, the results suggest that, dependent on the genetic predisposition to extremes in anxiety-related behavior, mice differentially interpret the odor of a potential predator, making this type of avoidance behavior highly predictable.

Dynamics of dopamine and norepinephrine contents in the dorsal hippocampus of rats during immunization with dopamine conjugate.

The dynamics of dopamine and norepinephrine contents in the dorsal hippocampus of rats immunized with a dopamine-BSA conjugate was studied during immobilization stress by mean of the microdialysis technique. Immunization with dopamine conjugate was accompanied by intensive production of antibodies against dopamine in rat blood and a tendency toward an increase in dopamine content in the dorsal hippocampus even in the basal state (before stress exposure). Under stress conditions, dopamine content in the dorsal hippocampus of immunized rats significantly increased. In control rats, stress was accompanied by a significant increase in norepinephrine content in the dorsal hippocampus. The observed peculiarities in dopamine and norepinephrine contents in the dorsal hippocampus of rats immunized with a dopamine conjugate were typical of active animals more resistant to emotional stress.

Stress reactions in rats during immunization to serotonin.

We studied the effect of immunization with a serotonin-bovine serum albumin conjugate on parameters of stress reaction to immobilization stress in rats. Active immunization was accompanied by changes in parameters reflecting animal resistance to emotional stress. The observed changes can be interpreted as a decrease in individual resistance to emotional stress. Active immunization of rats with a serotonin-bovine serum albumin conjugate was accompanied by production of autoantibodies against serotonin and dopamine. The role of autoantibodies against dopamine in modulation of the effect of immunization with serotonin-bovine serum albumin conjugate on the stress reaction in rats is discussed.

Hypothalamic and hippocampal release of serotonin in rats bred for hyper- or hypo-anxiety.

Microdialysis for measurement of serotonin in the paraventricular nucleus of the hypothalamus (PVN) and the dorsal hippocampus was performed under both basal and stimulated conditions, known to elicit differential behavioral and neuroendocrine responses in rats with inborn high (HAB) or low (LAB) anxiety-related behavior. We studied the release of hypothalamic and hippocampal serotonin in response to elevated platform exposure and forced swim stress, a mild emotional and a combined emotional and physical stressor, respectively. The data suggest that serotonin release patterns may depend on the inborn level of anxiety, the brain area dialyzed, and the stressor the animals were exposed to. Under basal conditions, no differences in serotonin release in either the PVN or dorsal hippocampus were observed between HAB and LAB rats. While in the PVN open platform exposure failed to change the release of serotonin, forced swim stress induced an increase in both HAB (p = 0.0001) and LAB (p = 0.01) rats with a significantly greater effect in the former (p = 0.027). In the dorsal hippocampus, only LABs, but not HABs, responded to the elevated platform exposure by enhancing the release of serotonin (p = 0.01). Also, forced swim stress increased hippocampal serotonin only in LAB (p = 0.002), but not HAB, rats probably indicating an involvement of hippocampal serotonin in locomotion and active stress coping. It remains to be shown to what extent the differences in serotonin release contribute to neuroendocrine and behavioral differences between HAB and LAB rats.