Effect of apomorphine on the wakefulness-sleep cycle of the common frog <Emphasis Type="Italic">Rana temporaria</Emphasis>

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist-apomorphine (APO)-at doses of 0.1, 1.0, 2.0, and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: the immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal muscle tones. These immobility forms are considered as homologues of mammalian stressreaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immobility state of the catalepsy type; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC there increased the portion of the sleep-like immobility state of the catalepsy type that is considered a functional homologue of sleep of homoiothermal animals. In spectra of electrograms of the frog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterior hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC certainly consists in that the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.     

Effect of apomorphine on the wakefulness--sleep cycle of the common frog Rana temporaria

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist--apomorphine-(APO) at doses of 0.1, 1.0, 2.0 and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: by immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal musculature tones. These immoboloty forms are considered as homologues of mammalian stress-reaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immoboloty state of the catalepsy; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC these increased the portion of the sleep-like immobility state of the catalepsy type that is considered as a functional homologue of sleep of homoiotherms. In spectra of electrograms of the flog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of the anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterioi hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC is unanimous: the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.     

Diencephalo-telencephalic changes of tyrosine hydroxylase in rats and grass frogs after sleep deprivation

Based on sleep deprivation-produced changes of electrographic parameters of the wakefulness-sleep cycle (WSC) in rats and frogs (Rana temporaria), 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. Changes in dynamics of tyrosine hydroxylase in rats and in frogs are revealed 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.     

Evolutionary aspects of sleep–wake cycle development in vertebrates (Modern state of the I.G. Karmanova’s sleep evolution theory)

The genetic basis of rest–activity circadian alternation in animal behavior is considered in the evolutionary range from bacteria to mammals. We scrutinize various concepts of sleep development in the animal world evolution as well as the I.G. Karmanova’s theory of the sleep–wake cycle evolution in vertebrates, beginning from wakefulness–primary sleep (or protosleep) in fish and amphibians through wakefulness–intermediate sleep in reptiles to wakefulness–slow wave sleep (SWS) and paradoxical sleep (PS) in birds and mammals. Primary sleep is represented by the three major sleep-like immobility states: catalepsy, catatonia and cataplexy. The main behavioral, somatovegetative and neurophysiological characteristics of primary sleep and the ancient activation pattern during primary sleep are described. The issues of which of these sleep manifestations are homologous to SWS, PS, hibernation and stress response are discussed. In conclusion, the general diagram of sleep evolution in vertebrates is presented, and the I.G. Karmanova’s contribution to evolutionary somnology is highlighted.     

Effect of photostimulation on the wakefulness-sleep cycle in the common frog Rana temporaria

Effect of daily 30-min photostimulation in the 10 s light: 10 s pause (the total of 5 days) on the time structure of the wakefulness--protosleep cycle (WPC) was studied in the common frog Rana temporaria. Changes were analyzed of EEG wave components in three immobility forms of the type of catalepsy (P-1), catatonia (P-2), and cataplexy (P-3) that form protosleep. The first three photostimulations promoted a gradual increase of the P-1 state to 84.16 +/- 11.6% [the initial value (IV) 22.9 +/- 9.1%] and a decrease of representation of wakefulness to 4.86 +/- 2/1% (IV 13.8 +/- 7.8%), of P-2 to 11.1 +/- 5.3 (IV 53.3 +/- 13.3%), and of P-3 to 2.21 +/- 1.0% (IV 11.1 +/- 5.6%). After 4-5 photostimulations and especially after their complete cessation the percentage of P-1 in the WPC was restored to initial values, whereas the percentage of the frog WPC P-3 considered to be a precursor of the homoiothermal sleep rose to 20 +/- 8.3% after 5 photostimulations and to 38.5 +/- 6.7% the next day. Changes in the frog EEG spectra appeared only after one photostimulation and were characterized by a brief increase of power of alpha-like waves and by inhibition of slow 6-waves. In P-2 the power of the slow delta-waves gradually rose. In P-3 the EEG parameters did not change. In all experimental animals a decrease of the relative thymus and adrenal masses was revealed, which indicates the photostimulation regime used in the work induces stress. The obtained data allow thinking that a certain neurohormonal response to stress has already been formed at the amphibian level and that an important role in this response realization is played by a coordinated interaction of the hypothalamic sleep-regulating system providing protosleep manifestations and of the hypothalamic neurosecretory system triggering the stress-reaction hormonal cascade.     

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.     

A new view on the role of phospholipids fatty acids: Possibility of electric charge transfer in the membrane monolayer

The fatty acid composition of phospholipids of subcellular fractions that are both generators and consumers of energy, mitochondria, synaptosomes, and myelin, has been studied in the brain and liver of several representatives of poikilothermal and homoiothermal vertebrates. The terrestrial poikilothermal animals have been shown to be close to homoiothermal animals by the main characteristics of membranes of the subcellular fractions, such as the content of saturated acids, the unsaturation index, and the ω3/ω6 acid ratio, but differ essentially from aquatic poikilotherms. The conclusion is made that the similarity in the fatty acid characteristics of the terrestrial poikilothermal and homoiothermal vertebrate membranes is due to their inhabitation in the oxygen-rich environment, while differences in intensity of the oxygen consumption are due to their different body temperatures. The models of structure of an arbitrary fragment of the lipid component of the studied trout membranes are presented, which illustrate a concept of a new functional role of fatty acids as participants of the electron transfer chain in the membrane.     

Effect of photostimulation on the wakefulness-sleep cycle in the common frog Rana temporaria

Effect of daily 30-min photostimulation in the 10 s light: 10 s pause regime (the total of 5 days) on the time structure of the wakefulness-protosleep cycle (WPC) was studied in the common frog Rana temporaria. Changes of EEG wave components were analyzed in three immobility forms of the types of catalepsy (P-1), catatonia (P-2), and cataplexy (P-3) that form protosleep. The first three photostimulations promoted a gradual increase of the P-1 state to 84.16 ± 11.6% (the initial value (IV) 22.9 ± 9.1%) and a decrease of representation of wakefulness to 4.86 ± 2.1% (IV 13.8 ± 7.8 %), of P-2 to 11.1 ± 5.3 (IV 53.3 ± 13.3 %), and of P-3 to 2.21 ± 1.0% (IV 11.1 ± 5.6%). After 4–5 photostimulations and especially after their complete cessation the percentage of P1 in the WPC was restored to initial values, whereas the percentage of the frog WPC P-3 considered to be a precursor of the homoiothermal sleep rose to 20 ± 8.3% after 5 photostimulations and to 38.5 ± 6.7% the next day. Changes in the frog EEG spectra appeared only after one photostimulation and were characterized by a brief increase of power of α-like waves and by inhibition of slow δ-waves. In P-2 the power of the slow δ-waves gradually rose. In P-3 the EEG parameters did not change. In all experimental animals a decrease of the relative thymus and adrenal masses was revealed, which indicates the stress nature of the photostimulation regime used in the work. The obtained data allow thinking that a certain neurohormonal response to stress has already been formed at the amphibian level and that an important role in this response realization is played by a coordinated interaction of the hypothalamic sleep-regulating system providing protosleep manifestations and of the hypothalamic neurosecretory system triggering hormonal cascade of the stress-reaction.     

Differences in macroglia of the spinal cord in various cold-blooded and warm-blooded animals

Certain macroglial differences of the spinal cord in poikilothermal (Rana esculenta, Lacerta agilis) and in homoiothermal (Columba livia, Felis domesticus, Macaca rhesus) animals have been revealed. A greater amount of glial satellites, surrounding neurons, motor centers of the spinal cord and appearance of new variety of astrocytes and oligodendrocytes are observed in the homoiothermal animals. It is supposed that the phenomenon mentioned indirectly reflects the evolutionary process of a more distinct functional differentiation of macroglia.     

Effect of experimental elevation and decrease of thyroxine level on catalepsy in rats

Thyroid dysfunction is associated with mental disorders. The present study was aimed to reveal the effects of experimental decrease and increase of thyroxine level on expression of two types of extensive freezing: spontaneous and pinch-induced catalepsy, in Wistar rat males. Chronic administration of thyroxine synthesis inhibitor, propylthiouracil (5 mg/kg/day, 28 days), markedly decreased plasma hormone level and at the same time produced a significant increase in percentage of spontaneously cataleptic animals and immobility time, but had no effect on the expression of pinch-induced catalepsy. On the contrary, chronic thyroxin (0.1 mg/kg/day, 28 days) treatment produced no effect on spontaneous catalepsy expression, although it significantly increased percentage of cataleptic animals and immobility time of pinch-induced catalepsy. The results suggest that both the thyroid hormone deficit and excess provoke catalepsy in rats but enhance different forms of freezing reaction.     

Manifestations of Dissolution of the Central Nervous System in the Wakefulness–Sleep Cycle of Mammals

The data are presented on three stages of formation of the wakefulness–sleep cycle (WSC) in representatives of poikilothermal animals (fish, amphibians, and reptiles), which are formed in accordance with morphofunctional stages of CNS integration. Comparison of morphofunctional development of brain structures in ontogenesis of mammals with dynamics of formation of the WSC neurophysiological parameters allows revealing similarity and parallelism in phylo- and ontogenetic stages of development of this cycle. All these results confirm the statement that in the process of transition from wakefulness to sleep there occurs a gradual rearrangement of activity of the evolutionary formed levels of CNS integration from the cortico-striatal to the bulbar integration. It is emphasized that unlike the known classical concept of CNS dissolution in pathological catastrophes in its activity, processes of periodical functional dissolution of CNS perform an important protective-restorative function and are vitally important to an organism.     

The wakefulness-sleep cycle in rats with a genetic predisposition to catalepsy

Neurophysiological studies on wakefulness-sleep cycle have been made in rats selected for hereditary inclination to catalepsy. It was shown that in these animals, the stage of delta-sleep is significantly reduced, whereas the duration of a superficial slow-wave sleep is increased. In a sleeping phase of the cycle, large amount of spindles in the range of alpha- and beta 1-oscillations was observed, especially significant in electrograms of n. caudatum and sensorimotor cortex. This activity is considered as a pathological manifestation of a transient hypnotic phase which includes the increase in immobilization of a cataleptic type.     

The effect of multiple audiogenic seizures upon the sleep organization in rats

The organization of sleep during and after frequentative convulsions, consisting of 2, 3, or 5 comparatively rare seizures (following one another with a 90-minute interval) or of 3, 5 or 9 comparatively frequent seizures (following one another with a 45-minute interval) of generalized tonic-clonic character in Krushinskii-Molodkina strain rats with inherited predisposition to audiogenic convulsions, was studied. In frequentative convulsions with rare seizures, between separate seizures, passive wakefulness (75.2 +/- 4.6% time) prevailed under low (24.8 +/- 4.3%) slow-wave sleep and full absence of fast-wave sleep. In rats under frequentative convulsions with frequent seizures, in interictal period, only passive wakefulness was observed under reduction of slow-wave sleep and fast-wave sleep, i.e. total sleep deprivation. Minimal latensy of first episodes of the slow-wave sleep after frequentative convulsions was 59.9 +/- 10.8, and of fast-wave sleep: 158.2 +/- 13.4 min. First episodes of slow-wave sleep and fast-wave sleep had normal structure, though they were lesser and shorter than in control experiments. In spite of long-lasting (up to 7 hrs) absence of slow-wave sleep during seizure and prolonged (8.5 hrs) reduction of fast-wave sleep with no subsequent compensatory increase, these conditions occurred in the wakefulness-sleep cycle during 12-hour reconstruction after convulsions. The reconstruction period after frequentative convulsions was characterized by increase in general share of wakefulness and reduction of total slow-wave and fast-wave sleep as compared with control data. Paroxysmal status seems to disorganize work of the brain somnogenic structures. The function of systems responsible for slow-wave sleep are affected to a lesser extent, but disorganization of the system responsible for fast-wave sleep is more significant and associated with mechanisms of starting the phase of sleep in the first place.     

Neurophysiology and analysis of the phenomenon of catalepsy

Neurophysiological mechanisms of the photogenic catalepsy (the "animal hypnosis"), genetic catalepsy, and cataplexy are discussed. The data obtained demonstrates a significance of the brainstem structures suppressing motor activity and the muscle tone in these conditions. Motor disorders associated with the general immobility are discussed from the standpoint of the evolutionary theory.     

Functional role of hypothalamic D1 and D2 receptors in organization of some forms of behavior of the common frog

Dopamine is one of the most ancient, widely spread neurotransmitters that performs a great number of neuromodulator effects in the vertebrate CNS. For the last few years there considerably increases an interest in study of functional role of this neurotransmitter in regulation of various forms of behavior of poikilothermal vertebrates. The present work deals with study of the role of the dopaminergic system, specifically of the hypothalamic dophaminergic system in providing some behavioral frog reactions. We studies behavior of the animals in the "open field" before and after administration to them of antagonists of D1 (SCH 23390) and D2 (haloperidol) receptors as well as of animals with destructed anterior and posterior parts of hypothalamis. Administration of SCH 23390 to intact frogs caused a statistically significant decrease of the number of exploratory reactions and goal-oriented jumps, whereas haloperidol only moderately increased the number of the above reactions. Destruction of the posterior part of hypothalamus inhibited essentially all kinds of activity, while destruction of the anterior part suppressed them completely. Antagonists of D1 and D2 receptors of dopamin little changed the initial motor and emotional activity of the operated animals. The obtained data are discussed in the light of evolutionary origin of D1 and D2 receptors in the vertebrate subphylum and allow concluding that D1 and D2 receptors of hypothalamic dophamin of the common frog are located predominantly in the anterior hypothalamic areas and that their effect on behavior can be mediated and is associated with other brain neurotransmitter systems in such brain structures as lateral hypothalamus, locus coereleus, and striatum that provide different aspects of wakefulness.     

Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans

The internal circadian clock and sleep-wake homeostasis regulate the timing of human brain function, physiology, and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis, and the light-dark cycle is crucial for optimal neurobehavioral and physiological function. Here, the authors show that the phase relationship between these factors-the phase angle of entrainment (psi)-is strongly determined by the intrinsic period (tau) of the master circadian clock and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time, and circadian period was estimated during a forced desynchrony protocol. The authors observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than did individuals with longer circadian periods. The authors also observed that light exposure history influenced the phase angle of entrainment such that phase angle was shorter following exposure to a moderate bright light (approximately 450 lux)-dark/wakefulness-sleep schedule for 5 days than exposure to the equivalent of an indoor daytime light (approximately 150 lux)-dark/wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.     

Bioenergetics of the lower vertebrates. Molecular mechanisms of adaptations to anoxia and hypoxia

In this review, causes of tremendous differences in respiration and oxidative metabolism between the homoiothermal and poikilothermal vertebrates are discussed. Tissues of the latter contain no lower, and sometimes even higher amount of mitochondria with the powerful potential of oxidative enzymes, as compared with the homoiothermal vertebrates; only 3–4% of this potential are realized due to a low rate of oxygen transport because of peculiarities of the cardiovascular system of the lower vertebrates. Limitation of the ATP synthesis provided a specific structure of plasma membranes with the much lower amount of channels for the passive ion leak as compared with the mammalian plasma membranes. Examples are presented of the homoiothermal animal cells (the frog olfactory receptor cell) that contact environment without participation of the blood circulation system and have the energy metabolism level comparable with that of mammalian cells. Examples of energetic aromorphosis are tunas with heat exchangers in several organs and with a powerful system of oxygen delivery to cells; owing to this, intensity of their oxidative metabolism could reach that of the higher terrestrial vertebrates. The closing part of this paper describes the molecular mechanisms that allow some representatives of reptiles, amphibians, and fish to survive long periods of hypoxia and anoxia.     

Wakefulness-sleep cycle and hypothalamo-pituitary system of young rat pups on the background of photostimulation

Effects of multiple photostimulations (PS) on behavioral reactions of the 30-day old rats were studied in the “open field” test, on the dynamics of the time EEG parameters of the wakefulness-sleep cycle, and on morpho-functional characteristics of the hypothalamo-pituitary neuroendocrine system. It has been revealed that PS promotes the gradual inhibition of the locomotor activity and exploratory behavior (p < 0.05) and an enhancement of autonomic reactions (p < 0.05) as well as an initial increase of intensity of orientation reactions with a subsequent decrease of their number (in connection with adaptation to a light stimulus), A comparative analysis of time parameters of the wakefulness-sleep cycle (WSC) shows a decrease of the part of wakefulness, the slow-wave and rapid-wave sleep phases with a simultaneous increase of the cataleptic stage and the sleep stage transient to the rapid-wave stage, as well as of the number of microactivations appearing on the sleep background at once after the several first PS. By the 4–5th photostimulations the CWS parameters on the whole are restored, except for the cataleptic stage, whose value remains statistically significantly high. The obtained data indicate the initial total CNS excitation and a decrease of the CWS stability. This conclusion is confirmed by the data of analysis of spectral characteristics of electrograms of cortical, hippocampal, hypothalamic brain parts and of caudate nucleus, which revealed only a brief small increase of δ-waves in the slow-wave sleep phase, but a statistically significant long decrease of power of the EEG δ-and ?-oscillations with a simultaneous power increase of α-components in the rapid-wave sleep. The quantitative parameters of changes of the morpho-functional state of neurosecretory cells of the hypothalamus supraoptic and paraventricular nuclei indicate the stress effect of this performed stimulation. The aspects of interaction of the hypothalamic-cortical and thalamo-cortical levels of the CWS integration on the background of chronic stress are discussed.     

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 82–88.Original Russian Text Copyright © 2005 by Vataev, Oganesyan.     

Dual manifestation of catatonic reaction in rats

Results of genetic, neurophysiological, neurochemical and pharmacological suggest that the cataleptic freezing and "nervousness" observed in the cataleptic rat strain GC have a common mechanism. There seems to be a physiological factor causing catalepsy, upon reaching a certain level of intensity, to be transformed into "nervousness", which is observed both at different period and/or moment of individual life and in the processes of breeding the strain for predisposition to catalepsy.