Involvement of the NO synthase system in stress-mediated brain reactions.

The neurosis-like state developing as a result of chronic stress in animals and accompanied by transient cerebral hypoxia can lead to significant impairments to many brain structures. The effects of the humoral components of the stress reaction on the brain are mediated by both extra- and intracellular signal pathways, among which nitric oxide (NO) is of great importance. We report here immunohistochemical studies of the expression of the constitutive neuronal (nNOS) and inducible (iNOS) isoforms of NO synthase in neurons in the brains of white rats in conditions of chronic stress leading to the development of a neurosis- like state. Chronic stress was found to induce increases in nNOS and iNOS expression in many parts of the brain, predominantly in the neocortex and hippocampus. Administration of the nonspecific NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) led to increases in the animals' depression, which was accompanied by reductions in motor and investigative activity assessed using traditional tests. This NOS inhibitor produced a minor increase in the expression of iNOS only. Thus, NO was shown to be involved in mediating the effects of stress with development of a neurosis-like state.

Blood testosterone in rats: correlation of the level of individual anxiety and its impairment after "death threat".

Studies of identical groups of male Wistar rats after preliminary selection to give groups including extreme behavioral types with low and high rankings on the anxiety scale showed that blood testosterone concentrations in intact rats (controls) correlated negatively with anxiety ranking, i.e., minimal hormone concentrations (no greater than 5 nM) corresponded to high levels of anxiety - with a predominance of passive defensive behavioral components on testing. Short-term exposure to a "death threat" situation (sight of a boa attacking and eating two individuals from the group of rats) impaired this correlational relationship in a manner comparable to the sequelae of chronic neuroticization by unavoidable pain stimulation. Impairments were manifest as scatter in measures in low-anxiety animals (3-21 nM). This characteristic, reflecting the multitude of adaptive pathways in the population in threat situations, distinguishes this type of action from neuroticization by unavoidable pain stimulation, which leveled out individual differences and decreased the hormone level.

A special case of learning disorder in isolant rats as a model of disintegration.

The combination of two factors - isolation and ontogenesis (starting from 21 days) and subsequent training of rats to a cyclical habit - could in some animals (30%) lead to the formation of unusual behavioral strategies consisting of maintenance of the cyclical habit without reinforcement with food. This dissociation from the vital motivation is regarded as an analog of the disintegration phenomenon, a key step in psychoneurotic disorders. The most common type of disturbance in isolated animals was suppression of searching activity, with extreme learning difficulty, though a training process including a two-month break led to a significant increase in motor-searching activity in this situation. These behavioral abnormalities were accompanied by morphological changes in the sensorimotor cortex of the brain, with a relative thinning of layer 5 and selective decreases in the density of satellite glial cells and deviations from the normal correlational relationships between behavioral and neuroglial measures.

Effects of chronic neuroticization on the monoaminergic systems of different structures in the brains of rats with different typological characteristics.

The levels of monoamines and their metabolites were studied by HPLC with electrochemical detection in homogenates of hypothalamus, hippocampus, prefrontal cortex, and amygdala in intact and neuroticized Wistar rats with different types of behavior in the open field and forced swimming tests. Intact rats with intermediate levels of activity and depressivity had higher serotonin concentrations in the hypothalamus and lower noradrenaline and hydroxyindoleacetic acid levels in the hippocampus than rats characterized by low activity and high depressivity. In neuroticization, the levels of study monoamines and their metabolites decreased in all the brain structures investigated with the exceptions of an increase in the dopamine concentration in the hippocampus and the dihydroxyphenylacetic acid concentration in the prefrontal cortex. The effect of neuroticization on the neurotransmitter systems in all study structures except the hypothalamus depended on the typological characteristics of the rats. This was most marked in rats with the extreme types of behavior--active and passive--in which changes in monoamine and metabolite contents were seen in all brain structures studied. Rats of the intermediate type showed no changes in any of the substances studied in the hippocampus.