Change of Parameters of Functioning of the Cardiovascular and Respiratory Systems in Rats of Different Ages under Effects of Low Doses of the Cholinesterase Inhibitor Phosphacol

In the 4-day old rat pups and adult animals there were studied effects of subacute and acute phosphacol intoxication at the doses producing and not producing inhibition of aetylcholinesterase on ECG parameters and respiration rate. Analysis of the heart rhythm variability (HRV) was performed using an original program designed in the Labview media. The frequency diapason of cardiointervals was divided as follows: the high-frequency component (HF)-0.8-2.5 Hz, the low-frequency (LF, waves of the II order)-0.8-0.3 Hz; frequencies lower than 0.3 Hz-VLF (slow waves of the III order). Under the conditions of the subacute intoxication the heart rate frequency in the 4-day old and in adult rats increases by 36% and 13%, respectively, the respiration rate frequency increases by 73% in the newborn and does not change in adult rats. The VHR analysis indicates an increase of the tone of the parasympathetic nervous system. The level of the sympathetic activity somewhat increases in adults, but decreases in the 5-day old rat pups, which leads to an essential shift of the vagosympathetic balance towards predominance of parasympathetic influences. In adult rats, unlike the newborns, the role of the humoral-metabolic factors in regulation of the cardiac rhythm and vasomotor reactions increases significantly. Remarkably, the decrease of the nervous sympathetic effects in the rat pups leads to the positive chronotropic effect and stabilization of the cardiac rhythm. Acute phosphacol intoxication (doses of 0.25 and 1 µg/kg) is studied in the 4-day old rat pups. The low dose of the drug leads to development of a moderate bradycardia without disturbances of the cardiac rhythm. The high phosphacol dose produces pronounced bradycardia; on its background there develops a long-term transitory arrhythmia representing complexes of the heart rhythm, which alternate in the decasecond or nearminute rhythm and are separated by periodicity that is one order slower. We observed such rhythm earlier during activation of central N-cholinoreactive structures and development of bilateral pneumothorax. Results of the present study allow stating the paradoxical heart rhythm not as agonic, non-peculiar to the “living” organism, but as a special form of functioning of cardiac pacemakers due to disturbances of the heart regulatory mechanism.__________Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 2, 2005, pp. 160–167.Original Russian Text Copyright © 2005 by Kuznetsov, Goncharov, Glashkina.     

Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the inter-systemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and manyminute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason—are weakly enhanced.     

Respiratory Cardiac Arrhythmia in Postnatal Ontogenesis of Rats

Development of the respiratory cardiac arrhythmia and the role of parasympathetic nervous system in its origin have been studied in rats aged from 4–6 days to 6 months of life. In rat pups of the first week of life, small fluctuations of cardiac rhythm were observed with the frequency close to fluctuations of respiratory rhythm. However, at this age they had neither regular character nor clear connection with phases of the respiratory cycle. On the 2–3rd week the amplitude of fluctuations rose and their association with respiration was established; however, unlike the respiratory arrhythmia observed in other animals and human, in rat pups there was deceleration but not acceleration of heart beating. By to the 6-week age the respiratory arrhythmia reached the maximal values, then its amplitude began to decrease. Bilateral transection of the vagus nerves in rat pups did not cause reduction of the respiratory arrhythmia. Thus, in rats the central influences on the heart can be transduced by bypassing the system of vagus nerves.     

Application of Cortexin for correcting the consequences of hypoxic-ischemic damage in the brain of infant rats

To verify if the peptide preparation Cortexin can be used to correct pathological processes in the CNS during perinatal ontogenesis, a set of physiological parameters (EMG, ECG, respiration, vagosympathetic balance) were recorded and analyzed in a rat perinatal hypoxic-ischemic brain damage (PHIBD) model and control infant rats. In experimental 7-day-old animals, PHIBD was modeled under inhalation ether anesthesia by ligation of the left common carotid artery and subsequent exposure to a gas mixture of 8% oxygen and 92% nitrogen. 1 h after exposure, animals were first injected intraperitoneally with cortexin (1 mg/kg); the preparation was then injected at a daily basis for 10 days. Both control animals and those after surgery but non-treated were injected with physiological solution. After 10 and 30 days after surgery, animals exhibited a delayed body weight gain versus control and significant differences in EMG intensity and spectral structure. Cortexin treatment induced on day 10 a transient improvement in EMG spectral structure but not amplitude; by day 30, the positive effect of cortexin was no longer observed. The respiration rate both in treated and non-treated animals was higher than in control. No significant changes in the heart rate were revealed in animals with PHIBD, but non-treated animals exhibited on day 30 a tendency towards its decrease. The heart rate variability (HRV) analysis showed that 10 days after trauma both non-treated and cortexin-treated animals exhibited a statistically significant shift in the vagosympathetic balance towards a parasympathetic prevalence. On day 30, cortexin treatment yields positive effects, while in non-treated animals the vagosympathetic balance shifts towards a humoral-metabolic and sympathetic prevalence. Cortexin injection to intact rats leads to significant disturbances in the vagosympathetic balance, cardiac and, to a lesser extent, respiratory rhythms, and can cause stable disturbances in activity of the somatic and vegetative nervous systems.     

Paradoxical Cardiac Rhythm in Rat Pups as a Possible Analog of the Sick Sinus Syndrome

Experiments with simultaneous recordings of ECG, electrogram of myocardial fibers of the right ventricle and neurogram of the right branch of vagus or sympathetic nerves were carried out on 3–18-day old rat pups. The electric activity recordings were performed under both in vivo and in situ conditions at unilateral or bilateral pneumothorax. It is established that the change in the cholinergic system activation level produced prior to pneumothorax decelerates the rhythm of cardiac contractions (CC) and induces periods of more frequent CC. After pneumothorax, this syndrome becomes more pronounced. The periods of alternation of the slow and fast rhythms may last for up to 1–2 min. The development of the pathological process leads to development of the sino-auricular and atrio-ventricular blocks. There appears a pattern of CC changes and complexes of the ventricular electric potentials that occur in decasecond and then in minute rhythms and are separated by periods of total asystole or preserved potentials of atrial excitation. When the electrograms of myocardium were recorded in rat pups under conditions of bilateral pneumothorax without any pharmacological intervention, it was possible to see a distortion of the sinus rhythm of CC developing for 2–2.5 h after respiration arrest and similar to the above-described distortion. The appearance and development of the phenomenon of the atypical cardiac rhythm is not directly related to the firing patterns of vagus and sympathetic nerves. At the same time, a correlation is clearly seen between the amplitude–frequency modulation of CC and discharges of vagus. A contraction of groups of respiratory muscles lasts for up to 30 min after pneumothorax, with occasional discharges seen in neurogram even after the complete immobilization of the animal. The development of the pathological process reveals a certain similarity with the phenomenon described in literature as the sinus node syndrome (tachy–bradycardia syndrome, TBS). Based on analysis of the cardiac rhythm transformation, it is suggested that the clinical TBS is a consequence of recapitulation, i.e., a successive release of ancient rhythms of excitation due to an impair of regulatory mechanisms.     

Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart beatings and respiration in ontogenesis

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneous motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations—secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart contraction rhythm within the limits of 10% of bradycardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.     

Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart rate and respiration in ontogenesis

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneos motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations--secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart beating rhythm within the limits of 10% of bradicardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.     

The effect of amniotic fluid taken from women in labor on the morphofunctional development of fetal and newborn rats]

Amniotic fluid from women was injected intra-amniotically to rats at the 14th day of pregnancy in a dose 0.3 ml. Morphological and functional parameters of embryonic development of rats and EMG activity of rat puppies at the age of 30-34 days differed from control ones with respect to the degree of maturity and motor disturbances of newborn babies. The data obtained reveal not only evident but also masked forms of motor pathology which was observed in children later, namely to 6-9 months. Chronic motor pathology in rat puppies was unilateral with central motor disturbances in babies being directly related to the degree of these disturbances.     

Motor Disturbances in Offspring of Female Ambidexter Rats with Psychogenic Trauma

The vital stress experienced by mothers both during and before their pregnancy produced motor disturbances in their offspring. By parameters of the EMG activity of the low extremities, more pronounced motor disturbances are revealed in the young 35-day old rat pups whose mothers were exposed to the acute psychogenic trauma during pregnancy. Asymmetry of the motor disturbances is the most prominent in the 45-day old rat pups born from the mothers exposed to the psychogenic trauma one month before pregnancy. In the process of ontogenetic development the revealed deviations are better compensated in the rat pups of the “neonatal stress” group than in the case of their mothers' preconception psychogenic trauma.     

Dysregulation of Autonomic Control of Cardiac Function in Workers at am Broadcasting Stations (0.738–1.503 MHz)

Ninety-three adult males working at AM broadcasting stations (0.738–1.503 MHz) or radio line stations volunteered for cardiological examinations. The examinations included routine electrocardiogram (ECG) at rest, analysis of heart rate variability (HRV), Holter 24-h ECG, and 24-h ambulatory blood pressure (ABP). Results of cardiological examinations were correlated with individual exposure to EM fields (maximum exposure levels during working shift, daily exposure dose, and cumulative lifetime exposure). Of the 93 subjects qualified for the study, 71 (76.3%) experienced occupational RF exposure, while the remaining 22 (23.7%) had no history of regular EM exposure. ECG abnormalities or pathological changes were recorded quite frequently (50–70%) in both exposed and control populations. There was no correlation with exposure levels. We found measurable effects in the HRV and ABP parameters in the EM-exposed population, but none could be assigned clinical significance. The results suggest that exposure of workers to EM fields can cause slight disturbances in autonomic cardiac regulation and slight dysregulation of circadian rhythms in workers exposed to EM fields exceeding 100–150 V/m.     

The blood glucose content in newborn rats depending on level and pattern of spontaneous motor activity

Earlier we have shown that administration to newborn rats of the pentose phosphate cycle inhibitor hydroquinone leads to a change in intensity and pattern of spontaneous periodic motor activity (SPMA) characteristic of early stages of development. The most typical was the disappearance of the rest period from the near-minute “activity-rest” cycle and the appearance of uninterrupted motor activity. In several cases, especially after 10 days of development, there was noted an enhancement in the SMPA pattern of the motor activity complexes following in the decasecond rhythm. In this study, on the 3–10-day old rats maintained under conditions of free behavior there was studied the blood glucose content in the animals at various periods of the activity-rest cycle. Apart from the SPMA phase, its composition (pattern) characterizing the maturity level and functional state of spinal motor centers was taken into account. In the 3, 7 and 10-day old rats at the rest period, the glucose concentration was established to differ depending on the motor activity pattern. In the case of the decasecond periodicity, it amounts to 5.7 ± 0.2, 6.3 ± 0.3, and 7.5 ± 0.3 mmol/l, while at the minute one—6.1 ± 0.4, 7.8 ± 0.3, and 7.8 ± 0.1 mmol/l. At the moment of bursts of motor excitation, the glucose concentration falls to 5.2 ± 0.1, 6.1 ± 0.4, and 7.1 ± 0.3 mmol/l at the decasecond and to 5.4 ± 0.5, 6.7 ± 0.2, and 7.6 ± 0.3 mmol/l at the near-minute rhythm (for the 3-, 7-, and 10-day old animals, respectively). The results obtained on the 5-day rat pups differ qualitatively from those observed in other age groups. Thus, the glucose concentration at the rest period amounts to 6.8 ± 0.2 at the decasecond and to 6.7 ± 0.4 mmol/l at the nearminute periodicity. At the period of motor excitation accompanied by the presence of the decasecond activity rhythm, the glucose concentration falls to the level of 6.0 ± 0.2 mmol/l by differing statistically significantly from the observed one in the rest state. In the case of the appearance of the minute rhythm, the glucose concentration amounts to 5.8 ± 0.3 mmol/l. The obtained data indicate that reproduction of the minute and decasecond rhythms recorded in composition of SPMA is accompanied by a change in the blood serum glucose level. The degree of a decrease of its concentration correlates with a certain activity rhythm: at the decasecond one the fall is 9, 13, 3, and 7%, whereas at the minute rhythm—11, 13, 14, and 2% (for the 3-, 5-, 7- and 10-day old rats, respectively). It is to be noted that a certain effect on the activity pattern is produced by the degree of satiety of the rat pups, the gastric emptying being accompanied by an increase in expression of the decasecond rhythm and of brief jerks. Besides, there occur the significant seasonal oscillations of the blood serum glucose concentration in the newborn rat pups—at the summer period it is statistically significantly higher than at the winter—spring period.     

Secondary rhythms of automatically functioning systems

In wakeful rats at the age from newborn to 3 weeks there were studied interrelations of rhythmical oscillations of heart rate, respiration rate, and periodic spontaneous motor activity. In all studied systems, these oscillations are coordinated and occur in several frequency diapasons. Frequencies in the near-minute diapason (the period from 30 to 90 s) are the most constant and do not change with age. Regular oscillations are the most stable in newborns. Bursts of motor activity usually are irregular, but episodically the distinct near-minute rhythm is traced. Studies of the character of interaction of the heart activity, respiration, and periodic somatomotor excitation allow stating that the main coordination pathway of spontaneous autorhythmic functions in early postnatal ontogenesis is formation of secondary rhythms. Possible ways of formation of the secondary rhythms are considered.     

Cardiac,respiratory, and motor activity in norm and after activation of catecholaminergic systems in newborn rat pups

Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the activity levels of dopaminergic and noradrenergic systems. To provide an excessive level of catecholamines, the animals were administered individually with L-DOPA (25–100 mg/kg) and with the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpirid). The L-DOPA administration produced a dose-dependent MA enhancement with its subsequent possible conversion into the continuous generalized activity. At P0 the release of monoamines was accompanied by development of weak bradycardia. There was noted a tendency for acceleration of respiration at administration of the low dose both of L-DOPA and of isoamine and for its deceleration at high doses. At P14 the L-DOPA administration was accompanied by deceleration of the heart rate (HR) by 8% and by acceleration of respiration rate (RR) by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of RR by 8% at the low dose and by 21% at the high dose of the agent. At the blockade of D1 receptors, RR remained close to the background values, while at the blockade of D2 receptors it decreased insignificantly. Blockade of D1 and D2 receptors did not cause significant HR changes. Analysis of the HR variability has shown that both after L-DOPA administration and at blockade of dopamine receptors no unidirectional reaction was observed: in 80% of rat pups the portion of nerve mechanisms of HR regulation increased, while in the rest-of sympathetic and humoral factors at a decrease of parasympathetic effects. In all rat pups the isoamine administration was accompanied by a shift of the specter power into the higher frequency area; in 60% of the animals there were enhanced sympathetic effects. At P14 in rat pups after administration both of L-DOPA and of isoamine, the sympathetic nervous effects were predominant. Thus, at P0 both at release of endogenous catecholamines and at their excessive concentration in rat pups there occurs a qualitative change of character of the catecholaminergic effects on functional activity of excitable structures, particularly of those connected with regulation of respiration.     

Natural environmental associations in a 50-day human electrocardiogram

Meteorotropic associations of heart rate (HR) and HR variability (HRV) were investigated in a clinically healthy 48-year-old man in Kiev. His electrocardiogram (ECG) was determined over 50 days by fitting him with an ambulatorily wearable device; various natural physical environmental variables were also monitored. The mean inter-beat interval, the standard deviation of these intervals, the spectral power in several frequency ranges, the power ratio of the approx. 10.5-s/approx. 3.6-s spectral components and other aspects of HRV were computed over consecutive 14.4-min intervals. Together with ordinary meteorological variables, geomagnetic disturbances (GMD) and fluctuations of atmospheric pressure (FAP) in the range 0.01–0.10 Hz (10–100 s) were measured. The assessable infradian spectra (with frequencies lower than 1 cycle/28 hours) of all HRV parameters showed two major components with periods of about 3.5 and 10 days. Two environmental variables, FAP and wind speed (with which FAP is closely related), revealed both of these rhythms and showed the greatest cross-spectral coherence (0.70–0.98) with corresponding oscillations of HRV. Less specific but statistically significant product-moment correlations with major HRV indices were also found; most of these were with FAP, but correlations with air temperature, humidity, wind speed and geomagnetic disturbances were also found. Long-term ECG recording, essential in the detection of infradian rhythms, proved to be sensitive to physical environmental variables, notably meteorological ones. FAP, usually neglected since its role has not been considered in previous biometeorological studies, or some factor closely related to FAP is probably involved in synchronizing or influencing the approximately 3.5-day HR and HRV rhythms in humans. Received: 27 July 2000 / Revised: 13 November 2000 / Accepted: 28 November 2000     

Comparative Evaluation of Heart Rate Variability Based on the Data of ECG and Blood Pressure Measurements

The development of new approaches to the assessment of heart rate variability (HRV) is an important problem, since HRV reflects the functioning of cardiovascular control and is affected by various diseases. The purpose of this study was to evaluate the informative value of statistical and spectral HRV parameters calculated from pulse interval (PI) data of blood pressure as compared with those calculated from RR-interval data of electrocardiograms (ECG). We recorded ECG in conscious rats using skin adhesive electrodes simultaneously with blood pressure signal obtained through a catheter in the femoral artery. It has been found that the PI sequence can be used to calculate the statistical HRV indices that describe the HRV at time intervals about 1 min or longer, but statistical indices of the PI and RR intervals may differ in the analysis of beat-tobeat variations. The power spectra of the RR intervals and PI coincide in the low-frequency region, including the band of baroreflex cardiac rhythm oscillation. However, they can differ in the high-frequency region (at respiration frequency and above).     

Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats

Circadian rhythms of behavior in rodents are regulated by a system of circadian oscillators, including a master light-entrainable pacemaker in the suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food-entrainable oscillators located elsewhere that generate rhythms of food-anticipatory activity (FAA) synchronized to daily feeding schedules. Despite progress in elucidating neural and molecular mechanisms of circadian oscillators, localization of food-entrainable oscillators driving FAA remains an enduring problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH) may function as a final common output for behavioral rhythms and may be critical for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9: 398-407, 2006). To determine whether the reported loss of FAA by DMH lesions is specific to one behavioral measure or generalizes to other measures, rats received large radiofrequency lesions aimed at the DMH and were recorded in cages with movement sensors. Total and partial DMH ablation was associated with a significant attenuation of light-dark-entrained activity rhythms during ad libitum food access, because of a selective reduction in nocturnal activity. When food was restricted to a single 3-h daily meal in the middle of the lights-on period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA persisted during a 48-h food deprivation test and reappeared during a 72-h deprivation test after ad libitum food access. The DMH is not the site of oscillators or entrainment pathways necessary for all manifestations of FAA, but may participate on the output side of this circadian function.     

Maternal control of the fetal and neonatal rat suprachiasmatic nucleus

The molecular clockwork underlying the generation of circadian rhythmicity within the suprachiasmatic nucleus (SCN) develops gradually during ontogenesis. The authors' previous work has shown that rhythms in clock gene expression in the rat SCN are not detectable at embryonic day (E) 19, start to form at E20 and develop further via increasing amplitude until postnatal day (P) 10. The aim of the present work was to elucidate whether and how swiftly the immature fetal and neonatal molecular SCN clocks can be reset by maternal cues. Pregnant rats maintained under a light-dark (LD) regimen with 12 h of light and 12 h of darkness were exposed to a 6-h delay of the dark period and released into constant darkness at different stages of the fetal SCN development. Adult rats maintained under the same LD regimen were exposed to an identical shifting procedure. Daily rhythms in spontaneous c-fos, Avp, Per1, and Per2 expression were examined within the adult and newborn SCN by in situ hybridization. Exposure of adult rats to the shifting procedure induced a significant phase delay of locomotor activity within 3 days after the phase shift as well as a delay in the rhythms of c-fos and Avp expression within 3 days and Per1 and Per2 expression within 5 days. Exposure of pregnant rats to the shifting procedure at E18, but not at E20, delayed the rhythm in c-fos and Avp expression in the SCN of newborn pups at P0-1. The shifting procedure at E20 did, however, induce a phase delay of Per1 and Per2 expression rhythms at P3 and P6. Hence, 5 days were necessary for phase-shifting the pups' SCN clock by maternal cues, be it the interval between E18 and P0-1 or the interval between E20 and P3, while only 3 days were necessary for phase-shifting the maternal SCN by photic cues. These results demonstrate that the SCN clock is capable of significant phase shifts at fetal developmental stages when no or very faint molecular oscillations can be detected.     

Thermoregulation and diurnal rhythms in 1-week-old rat pups

This paper reviews the ontogeny of thermoregulation and diurnal rhythmicity in rats. Additionally, original data are presented that indicate the emergence of an endogenous circadian core temperature rhythm during the first postnatal week. Despite neurological immaturity, newborn rats display autonomic and behavioral thermoregulatory responses within 24 h of birth. Their "biological clock" is already running before birth. The thermal environment of pups changes cyclically owing to diurnal variations in maternal behavior, but the core temperatures of 1-week-old pups huddling in the absence of the dam also show marked diurnal fluctuations. Five- to 8-day-old lean Zucker rat pups artificially reared in the absence of 24-h cycles of ambient temperature and food intake show diurnal changes in core temperature similar to those in huddling mother-reared pups. Diurnal core temperature changes, evident only when regulatory effectors are not overwhelmed, are one of the first self-maintained diurnal rhythms to appear. Because thermoregulation and circadian rhythmicity both appear before maturation of the neural networks believed to be critical for their control in adult animals, studying the immature rat might increase our understanding of the control of these processes in the more complex mature central nervous system.     

The process of cardiorespiratory autoresuscitation in intact newborn rats

To examine the process of spontaneous autoresuscitation and the recovery of the hypoxic ventilatory response (HVR) after prolonged anoxia, we monitored respiratory frequency (f, by body plethysmography) and heart rate (HR, by ECG) in intact newborn rats (n = 12, day 2-4) before, during, and after 100% N2 exposure. The rat before anoxia showed signs of HVR: f changes at acute hypoxia (10% O2) and hyperoxia (100% O2). During anoxia, the spontaneous respiratory movement "gasping" appeared for 21 min (mean). At O2 restoration (with 100% O2), gasping stopped and no respiratory flow was detected for 1 min. One rat failed to autoresuscitate and had heart arrhythmia during the transient apnea, but 11 rats recovered respiration after the HR acceleration. Despite the successful autoresuscitation, the rats did not show HVR at 10 min into the recovery period and the recovery of HVR required more than 30 min. The results indicate that O2 inhalation is useful to trigger autoresuscitation even when the rat has already been in a state of profound hypoxic depression, but the rat becomes transiently insensitive to HVR after autoresuscitation. We estimate that reform of the respiratory control system in newborn rats is not yet firmly established to track HVR early in the recovery phase after prolonged anoxia.     

Age-related changes in activity of cerebellum Purkinje cells,shape of the complex spike,and locomotion of Wistar rats under effect of ethanol

The work deals with study of peculiarities of effect of ethanol upon the Purkinje cell activity, shape of the complex spike, and locomotion of rats at different stages of ontogenesis, such as the stage of the morphofunctional maturation of the cerebellar cortex, the mature stage, and in the process of aging. The experiments were carried out on three age groups of Wistar rats: rat pups (2 weeks), adult rats (3–6 months), and senile animals (22–26 months). The administration of ethanol has been established to produce an increase in frequency of simple spikes, a decrease in frequency of complex spikes, a shortening of duration of depression of simple spikes, a decrease in the total duration of the complex spike, the number and frequency of its impulses as well as reduction of the motor activity of animals of all age groups. The change of the majority of the studied parameters occurred by the common temporal scheme. The earliest responding were the rat pups, later-the adult rats, and the last-the animals of the senior group. The stronger effect of ethanol was observed in adult rats. Their differences of all studied parameters, as compared with rat pups and senile animals, were characterized on the whole by the longer period of time and by the higher percent of changes relative to the initial values. Analysis of the obtained results has shown that the most pronounced changes in parameters of the cerebellum Purkinje cell activity and of the complex spike shape corresponded to the more significant decrease in the locomotion level, i.e., were recorded in adult rats. Thus, the work has demonstrated different sensitivity to administration of ethanol in the Wistar rats at different stages of ontogenetic development.