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As part of the urinary concentrating mechanism, renal inner medulla cells may be exposed to extremely variable NaCl and urea concentrations that can reach very high levels. A number of studies, reviewed herein, aim to understand how such osmotic stress affects the cells and what protective mechanisms might exist. The majority of these studies are done on inner medullary epithelial cells that grow continuously in tissue culture (mIMCD3). Cells grown at 300 mosmol/kg survive increase to 500 mosmol/kg by adding NaCl or urea, but only after a growth arrest of approximately 24 h. At a higher osmolality (650-700 mosmol/kg) most cells die within hours by apoptosis. The cells both in vitro and in vivo adapt to high osmolality by a number of mechanisms, including accumulation of variety of organic osmolytes and induction of heat shock proteins. The cell cycle delay results from blocks at the G1 and G2/M checkpoints and slowing during S. After adding NaCl, but not urea, the amount and transcriptional activity of p53 (the tumor suppressor protein) increases. The p53 is phosphorylated on ser-15 and is transcriptionally active at 500 mosmol/kg (associated with cell survival), but not at 700 mosmol/kg (associated with apoptosis). Reduction of p53 expression by p53 antisense oligonucleotide increases sensitivity of renal cells in culture to hyperosmotic stress caused by NaCl. The possible mechanisms of the protection action of p53 against hypertonic stress are discussed.

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This study tested the hypothesis that endogenous digitalis-like factor (DLF) is involved in the development of alcohol dependence in rats. In 33 male Wistar rats in conditioned place preference (CPP) experiment, ethanol evoked increase in time spent in the ethanol-associated compartment (702+/-82 in ethanol-treated vs. 426+/-86 sec in the controls). Digoxin pretreatment (125 microg/kg, i/p) did not affect the time spent in the water-associated compartment (476+/-80 sec), but prevented the acquisition of ethanol CPP (385+/-112 sec in ethanol-paired side, P<0.05). In a two bottle choice test, where rats (n=6 per group) chose between drinking water and 9% ethanol, immunization against two putative DLFs, marinobufagenin and ouabain (MBG and OLC) resulted in a 60% increase of ethanol consumption. Acute intragastric administration of 9% ethanol to the rats was associated with increased OLC in cerebrospinal fluid, and stimulated urinary excretion of MBG and OLC. Thus, in rats, digoxin, which mimics the effects of DLFs, suppresses the free choice of alcohol, while immunization against DLFs is associated with alcohol seeking behavior.

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Genistein was shown to potentiate the effects of all the activators of the water flow except the cAMP action. The thyrosine kinase (TK) seems to suppress the hydrosmotic action of arginine vasopressin at the period preceding the cAMP formation and to potentiate this effect afterwards.

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The role of protein kinase C (PKC) in the control of vasopressin-stimulated water transport in the frog urinary bladder and its modulation by M2-agonist oxotremorine has been studied. Using the PKC inhibitor, staurosporine we showed that PKC in the region pf the basal membrane suppressed vasopressin-stimulated water transport, whereas PKC in the apical region potentiated this transport. It was also found that from the two types of oxotremorine action on stimulated water transport determined by its concentration only inhibition is mediated through PKC.

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24-hr isolation of newborn rats from mother decreases their body weight and growth of the brain mass. The fiber cerebral structures are delayed in their development in deprived newborn rats. Thyroid gland also becomes altered resulting in its hypofunction. The data obtained suggest that the neonatal isolation is a strong stress delaying rather considerably development of a number of cerebral structures, leading to endocrinal disfunction and altering the behaviour.

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Thyroid morphology, function, and hormonal levels were studied in two rat strains with genetically determined levels of nervous system excitability immediately and in late periods after prolonged stress resulting in development of a neurosis-like state. A high resistance of the linear characteristics of thyroid morphology and function was revealed whose high functional activity was observed in the rats with a low excitability threshold. Two weeks after neurotization cessation morphofunctional status of the thyroid normalized.

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The authors have shown that rat strains with varied excitability of the nervous system also differ in thyroid morphofunctional features. Selection based on the nervous system excitability threshold resulted in divergence of reactivity of the endocrine system (the thyroid) to prolonged stress.

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Rats with spontaneous hypertension (strain SHR) reveal retarded somatic growth at early stages of ontogenesis. However, in further postnatal life, after transition to self-feeding, these animals exhibit larger body mass. Significant correlation was found between the arterial pressure and body mass. Some peculiarities in the behaviour of rats from the strain SHR were found already at early stages of ontogenesis. In 2-month animals, the brain exhibits some unusual features: lateral ventricles are enlarged, the corpus callosum is thinner, the volume of the pyramids in the dorsal hippocamp (field CA3) is less than in normal rats, the structure of the lateral hypothalamus being also different. It is suggested that unusual behaviour of hypertensive strain is due to the observed structural differences, as well as to changes in noradrenergic system of the brain.

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Electrophysiological, morphometric and behavioural studies have been made on the role of parafascicular complex in regulation of nociceptive sensitivity in 45 rabbits from the 1st to the 16th day of their postnatal life. The evoked potential to nociceptive stimulation was recorded already in 1-day animals. Analysis of amplitude-temporal parameters of the EPs in acute experiments revealed a sharp increase in their positive phase at the 7-8th day of life. As it was shown in the behavioural experiments, that is just the period of maximum generalized reaction to nociceptive stimulation. It was found that to this age, the surface of neurones in the complex significantly increases, their density remaining still high. The data obtained are discussed in relation to factors which account for ontogenetic changes in electrophysiological correlates of neuronal responses in the parafascicular complex to peripheral nociceptive stimulation.

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Original data together with those from literature are presented concerning structural peculiarities of the hippocamp in rats and mice. Structural differences are revealed not only in these species, but in separate strains from a single species. Fine structural differences may account for different modes of realization of the behavioural reaction.

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Neuromorphological and behavioural studies have been made on several strains of mice (C57B1, DBA/2, SEC) and on the spiny mouse Acomys cahirinus. It was shown that animals with different genotypes differ by the size of fascia dentata and by the extension of the pyramidal layer in CA3 field of the hippocamp. Animals with a higher learning capacity exhibited smaller layer of granular cells in the fascia dentata, which may be due to a lower density of neurones in this region. Terminals of the mossy fibers--the axons of granular cells--were found mainly on the apical dendrites of the pyramidal cells in CA3 field. On the contrary, in animals with lower capacities to learning, mossy fiber terminals were observed mainly on the basal dendrites of the pyramidal cells, the extent of the granular layer in these animals being significantly larger.

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Morphological studies have been made of the neocortical and archicortical structures in the spiny mouse Acomys cahirinus, the only maturely born species from the family Muridae. The data obtained reveal highly developed hippocampus as compared to the neocortex in this mouse, in contrast to relationships found in other mice and rats.

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As a result of selection of rats possessing a high threshold of neuro-muscular exitability in comparison with rats possessing a low threshold of neuro-muscular exitability, certain changes take place in the structures that are connected with the learning process: the visual cortex is wider, volumes of the pyramidal cells in the fields CA1 and CA3 of the hippocampus are increased, density of the glial elements in the fornix is essentially increased and that of neurons in the septal nucleus is decreased.

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