[Inferior colliculus stimulation effects in KrushinskiI-Molodkina strain rats].

The effects of the central nucleus of the inferior colliculus chemical and electrical stimulation on the producing and forming the convulsive manifestations, as well as on the organization of sleep, was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Microinjections of quinolinic acid (10 micrograms) or electrical stimulation with 70 Hz frequency produced the paroxysmal manifestations in the form of intensive circular excursions coincident wild running behaviors on the initial nonseizures motor exitation stage of audiogenic seizures. The results suggest that in Krushinskii-Molodkina strain rats the inferior colliculus is involved in the neuronal network, responsible for initiation and realization to the scampering stage of the evoked convulsive reactions to sound. The reduction of fast-wave (paradoxical) sleep total duration after the given actions it was observed. However, the inferior colliculus electrical stimulation with 7 Hz frequency during slow-wave sleep cause appearance the episodes fast-wave sleep. A significant (almost twice due) increase of the total time of fast-wave sleep by increasing the quantity, but not the duration of these episodes after 3-4 sessions of such sort stimulations were observed. These results showed that the inferior colliculus rats can produce the modulating action on the brain system responsible for triggering fast-wave sleep.

[The action of ionotropic glutamate receptor channel blockers on effects of sleep deprivation in rats].

The action of non-competitive glutamate receptor antagonists on the effects of sleep deprivation has been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar rats deprived to this respond. Two types of glutamate receptor open channels blockers were used: the selective blockers of NMDA-receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA- and presumably Ca(2+)-permeable AMPA/kainate receptors (IEM-1754 and IEM 1925). Rats were subjected to 12 hours long sleep deprivation. Immediatly after that memantine and IEM-1921 were injected, and during the first 3 hours the total or partial reduction of fast-wave (paradoxical) sleep and a significant increase of the representation of wakefulness at the cost of reducing the total time of slow-wave sleep were observed. These effects are most likely to be a consequence of the blockade of NMDA-receptors functioning in the systems of the rat brain responsible for the launch and maintenance of fast-wave sleep. Injection of IEM-1754 and IEM-1925 on background of sleep deprivation did not affect the organization of sleep during the first 3 hours of their action. During the second three-hour period the rebound effect was observed. The obtained results indicate the involvement of NMDA glutamate receptors in the functioning of various parts of the sleep system of both rat lines.

[Effects of ionotropic glutamate receptor channel blockers ON sleep-waking organization in rats].

The effects of non-competitive glutamate receptor antagonists on sleep-waking organization have been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar ones which are resistant to this action of sound. Two types of blockers of glutamate receptor open channels were used: selective blockers of NMDA receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA and Ca-permeable AMPA/ kainate receptors (IEM-1754 and IEM 1925). During the first 3 hours after administration of these glutamate antagonists the total or partial deprivation of fast-wave sleep was provoked. Additionally the selective NMDA receptor blocking drugs (memantine, IEM-1921) induced in the same period a significant increase of the representation of wakefulness at the cost of reducing of the total time of slow-wave sleep. These effects are most likely to be a consequence of the blockade of NMDA receptors responsible for the launch and maintenance of wakefulness, slow- and fast-wave sleep. In the same first 3 hours period after the administration of IEM-1754 and IEM-1925 the organization of sleep was not significantly affected. The evident reduction of wakefulness, total duration and increase of slow-wave sleep impact was observed, during the second three-hour period. It, apparently, can be caused by the blockade of AMPA/kainate receptors. The obtained results indicate the involvement of NMDA and AMPA/kainate receptors in the functioning of various parts of the sleep system of rats belonging to both lines.

[Raction of dopaminergic and vasopressinergic systems in sleep deprivation in rats].

Six hours sleep deprivation experiments were carried out on rats after threefold injection of D1 dopamine receptor antagonist SCH 39 166. Immunohistochemical study of striatum revealed the increase in D1 and D2 dopamine receptor and glutamate immunoreactive material during the sleep deprivation and 2 h of postdeprivation period. The level of AMPA glutamate receptors increased under the sleep deprivation and decreased in the postdeprivation period. The data obtained are discussed in association with dynamic of changes of vasopressin immunoreactivity in neurosecretory supraoptical and paraventricular nuclei of hypothalamus in these experiments and in experiments without D1 receptor antagonist pretreatment.

[About evolution of sleep-wakefulness cycle in vertebrates].

Data about behavioral, somato-vegetative and neurophysiological parameters of sleep and wakefulness in insects, cold- and warm-blooded vertebrates are provided. Hypotheses existing now about evolutionary formation of separate sleep phases and stages in vertebrates are considered. In the review are shown the data about correlations of quantitative characteristics of sleep and wake in some mammals with basic metabolic rate, lifestyle, environmental habits. The original experimental results at formation of neurophysiological characteristics of sleep and wake in vertebrates, phylogeny and in ontogeny of mature and immature mammals are provided in detail. On the basis of own concepts about evolutionary development of sleep-wakefulness cycle in vertebrates the interactions of telencephalic, diencephalic and rhombencepalic parts of brain in the processes of cycle wakefulness cycle integration are discussed.

[On filo- and ontogenetic development of dopaminergic regylation of wakefulness-sleep cycle in vertabrates].

The comparative immunohistochemical researches of dofamine containing neurons and fibers are carried uot in telencephalic and diencephalic departments of the brain in different vertebratts (adults rats, rats aged 14 and 30 days and frogs). For analysis of quantitative changes dynamics in thyrozinhydroxylase, D1 and D2 immunoreactive material in sleep-wakefulness cycle the model of sleepdeprivation is used. There are found the facts of morphofunctional correlations in the reactions of dophaminergic system during ontogeny and phylogeny. Besides, the pharmacological effects of dofamine agonist and antagonists on the sleep-wakefulness cycle in young rats and in frogs are shown. So, dopamine and its agonist apomorphine increase in sleep-wakefulness cycle duration of sleep-like state ofcataplexy (homolog of the sleep) in frogs, in 30-day-old rats it increase the share of wakefulness and catalepsy. D1 receptors antagonist (SCH 23390) adminisrated to frogs, caused increase of wakefulness and catatonic type states duration, where as D2 receptors antagonist (apomorphine) increased cataleptic condition. Administration of dopamine antagonist (haloperidol) to 30-day-old rats previously causes the increase of cataleptic state, after which the slow wave sleep state is enhanced. The questions of phylo-, ontogenetic formation of dopaminergic system regulating role in sleep-wakefulness cycle, when transition mainly from neurosecretory diencephalic influences of dophamine to the mainly neurotransmittory functins of telencephalic regions occured, is discussed.

[Participation of vertebrate forebrain activating systems in organization of the wakefulness--sleep cycle].

The article considers mechanisms of diencephalic-telencephlic interactions in regulation of the wakefulness-sleep cycle in various classes of vertebrates. In such interactions a special role is played by the dopaminergic systems that perform neurosecretory function at the level of diencephalon and neurotransmitter function at the level of telencephalon. Concepts of A. I. Karamyan and A. L. Polenov about the stage pattern of development of CNS and neurosecretory systems are presented as well as the interconnection of dopaminergic and glutamatergic neurotransmitter system in the mammalian neostriatum in the wakefulness-sleep cycle is considered. Comparison of dynamics of expression of the dopamine metabotropic receptors and of the glutamate ionotropic receptors in neostriatum showed unidirectional changes of D1 and AMPA on the background of the 6-h sleep deprivation as well as of D2 and NMDA on the background of postdeprivative sleep. The corticofugal direction of glutamate impulsation and its relatively fast actions allow admitting its triggering action on generation of the sleep-inducing processes in the underlying brain parts.

[Methods of non-linear dynamics in estimation of electroencephalograms of healthy people and of patients with epilepsy].

A possibility is discussed of use of methods of non-linear dynamics for analysis of spontaneous EEG and if the EEG caused by low acoustic stimuli in healthy people and in patients with epilepsy. A use of methods of non-linear dynamics--the fractal dimension of EEG--in clinical practice and in research is described.

[The sleep organization in the Krushinskii-Molodkina strain rats after sleep deprivation and different intensity audiogenic seizures].

Organization of sleep after different intensity audiogenic paroxysmal seizures evoked in animals under normal diurnal wakefulness-sleep cycle and after 12-hour fast-wave sleep deprivations or 6-hour total sleep deprivation was studied in Krushinskii-Molodkina strain rats with an inherited predisposition to audiogenic convulsions. Under all specified conditions, intensive audiogenic clonic or clonic-tonic convulsions caused long-lasting and pronounced sleep disorders in rats associated with disorganization of the mechanisms of starting the fast-wave sleep phase in the first place. But after experimental deprivations of sleep the audiogenic paroxysmal seizures run only as initial motor excitement without obvious convulsions. Such sort of seizures promote a faster beginning of recovery process after deprivations and did not cause any disorganization of the function of the brain systems responsible for starting and shaping (maintenance) fast-wave sleep.

[Effects of memantine on convulsive reactions and sleep-waking cycle in Krushinskii-Molodkina strain rats with the inherited predisposition to audiogenic convulsions].

Krushinskii-Molodkina strain rats have an inherited predisposition to audiogenic convulsions and are used as a natural animal model in the anticonvulsive drugs studies. We have investigated whether changes in the glutamatergic synaptic transmission are involved in the mechanism of audiogenic convulsions and functional organization of sleep-waking cycle observed in rats of this line. For this purpose Memantine, a selective uncompetitive blocker of NMDA receptors was used. Memantine was injected i.m. at the dose 5 or 10 mg/kg injected 30 min, 1, 2 or 3 hours before the sound stimulus (the sine-wave tone 8 kHz, 90 db). We evaluated the latent period of initial enhanced motor activity, the appearance and intensity of clonic seizures, and thereafter the tonic seizures accompanied by extension of limbs and tail. The maximal attenuation of convulsive attack to the level of initial motor excitement only was occurred in 60% of rats between 1 and 2 hours after memantine pretreatment. No difference between the doses 5 and 10 mg/kg was observed. The effect of memantine began to decrease when memantine was injected 3 h before convulsion provocation. The recording of EEG by chronically implanted electrodes was performed from the rats of Krushinsky-Molodkina line for the study of memantine effects on the sleep organization. The sleep of these rats during the first hour after 5 or 7 mg/kg memantine injection exhibited as the short periods of slow-wave sleep only which disappeared completely thereafter 54.4 +/- 4.9 and 39.9 +/- 5.2 min correspondingly. The complete sleep loss was observed approximately 2-2.5 hours later and followed by appearance of episodes of slow-wave sleep. The first episodes of fast-wave sleep occurred 3-4 hours later. Their reappearance evidenced of the completion of memantine action on the somnogenic brain systems and the beginning of recovery of normal sleep-waking organization. Thus the manifestations of unidirectional and synchronous memantine action on audiogenic seizures and disturbances of sleep-waking mechanisms may speak about involvement of NMDA receptors in both of epileptogenesis and somnogenic system of Krushinsky-Molodkina rats line.

[Dissolution of the wakefulness-sleep cycle in patients with catatonic form of schizophrenia].

Polysomnograms of two patients with catatonic form of schizophrenia of different duration of the disease were recorded and analyzed. Pronounced disorders of the wakefulness-sleep cycle (WSC) were revealed. Apart from differences connected with duration of the disease and treatment with corresponding medications, there were detected the general features indicating dissolution of the central nervous system and the very wakefulness-sleep cycle. A certain similarity of the found WSC disturbances with the earlier shown WSC disturbances in rats with predisposition to catalepsy was noted. The conclusion is made about domination of diencephalic influences over the telencephalic one in the studied patients.

[Effects of transliquoral electrical brain stimulation on the wakefulness-sleep cycle in rats].

Peculiarities of natural behavior in unanesthesired Wistar strain rats, and their electrogram patterns under the liquor brainstem electrical stimulation were in the focus of present study. Analysis of the electrogram specters of somatosensory and auditory areas of the cortex, hippocampus, mediodorsal thalamic nucleus, lateral periaqueductal gray and fastigial cerebellar nucleus revealed authentic increasing of teta-waves most significantly during slow-wave sleep period under the electrostimulation. The increasing of complete wakefulness-sleep cycles was found after multiple (15-20 per hour) stimulations. Possible homeostatic effect of the liquor brainstem electrical stimulation on somnogenic mechanisms are discussed.

[Dopaminergic system in the telencephalic and diencephalic brain regions in vertebrates in the sleep-wakefulness cycle organisation].

The aim of our study was to investigate the role of dopaminergic system in telencephalic and diencephalic brain regions of vertebrates in sleep-wakefulness cycle. The level of thyrosine-hydroxylase--the main enzyme in dopamine synthesis--was measured in striatum, zona inserta supraoptic and arcuate nuclea of hypothalamus in fish (Acipenceridae) and in mammals (rats) in ontogenesis (14-, 30-day old rats and adult animals) under tactile and sleep deprivation stresses. The thyrosine-hydroxylase-immunoreactive cells were revealed in all brain regions of fishes after a short-term stress. In the group after longtime stress, the thyrosine-hydroxylase-immunoreactive cells and fibers were almost absent in anterior brain but were found in hypothalamic nuclea. At 14-day old rats, 2-hour sleep deprivation caused increasing of thyrosine-hydroxylase-immunoreactivity both in fibers of caudate nucleus as well as in cells of the zona inserta. A 6-hour deprivation caused increasing of thyrosine-hydroxylase-immunoreactive material level in cells of zona inserta and decreasing it in fibers of 30-day old rats. In adult rats, the level of thyrosine-hydroxylase-immunoreactive material decreased in nucleus arcuatus and zona inserta after sleep deprivation and increased after sleep. Data obtained are discussed in terms ofphylo- and ontogenetic development of neurosecretory and neurotransmitter functions of dopaminergic system in evolutionary old diencephalic and evolutionary young telencephalic brain regions of vertebrates, which are the important systems of starting and maintenance of some functional conditions of the organism in sleep-wakefulness cycle.

[Diencephalo-telencephalic changes of tyrosine hydroxylase in rats and common frogs (Rana temporaria) after sleep deprivation].

Based on sleep deprivation-produced changes of electrographic parameters of the wakefulness--sleep cycle (WSC) in rats and common frogs, dynamics of activity of tyrosine hydroxylase, the key enzyme of dopamine synthesis, was studied immunohistochemically in substantia nigra and nigrostriatal pathway in rats and in striatum, paraventricular organ, and extrahypothalamic pathways in frogs. There are revealed changes in dynamics of tyrosine hydroxylase in rats and in common frogs after the 6-h sleep deprivation and after 2 h of postdeprivation sleep. This allows determining the degree of participation of corticostriatal neuroregulatory and hypothalamo-pituitary neurosecretory systems and their role in regulation of WSC. Possible evolutionary peculiarities of morphofunctional differences in homoiothermal and poikilothermal animals are discussed.

[Effect of swinging on EEG of rats of juvenile age in the wakefulness state].

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.

[Electroencephalographic analysis of manifestations of latent forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats].

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of a-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. It was shown the long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of theta-diapason oscillations and with an increase of representation of alpha-diapason waves on EEG in the state of the animal quiet consciousness. A role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.

[The effect of dopaminergic nigrostriatal system on sleep deprivation in rats].

The analysis of the electrophysiological features of sleep-wakefulness cycle in Wistar rats for 9h after a 6h sleep deprivation was carried out. The delay of sleep rebound (since 2.5-3 h after deprivation) was found in the form of moderate increasing of slow-wave sleep and fast-wave sleep phases. According to these sleep-wakefulness cycle changes, a quantitative immunohistochemical study of tyrosine hydroxylase: a key enzyme of dopamine synthesis--and D1 and D2 receptors in nigro-striatal projections has been performed. After sleep, an elevation of D1 receptors immunoreactivity in caudate nucleus and reduction of tyrosine hydroxylase immunoreactivity in compact part of substancia nigra was found. After postdeprivation sleep, a decrease of D1 receptors immunoreactivity and increase of D2 receptors immunoreactivity in caudate nucleus together some increase of tyrosine hydroxilase immunoreactivity in substancia nigra compacta has been observed. These data can testify about active role of dopaminergic nigrostriatal system which provide at the same time with another neurotransmitters of the central nervous system the telencephalo-diencephalic interaction in sleep-wakefulness-sleep cycle.