Galanin of the homologous species inhibits insulin secretion in the rat and in the pig.

It is known that pig galanin inhibits insulin secretion in dogs, rats and mice. The present study examined whether species-specific, homologous, galanin inhibits insulin secretion. Thus, the effects of rat galanin were examined in the rat, and the effects of pig galanin were examined in the pig, both in vivo and in vitro. In conscious rats, synthetic rat galanin (2 nmol kg-1) abolished the glucose- (0.56 mmol kg-1) induced increase in plasma insulin levels. In vitro, rat galanin (10(-9) to 10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated rat islets. In anaesthetized pigs, 15 min infusion of synthetic pig galanin (207 pmol min-1) into the pancreatic artery decreased the insulin output with a subsequent recovery. In vitro, pig galanin (10(-6) mol l-1) inhibited glucose- (8.3 mmol l-1) stimulated insulin release from isolated pig islets. We conclude that homologous galanin inhibits insulin secretion in both the rat and the pig.     

The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep

Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep–wake profiles of neonates in the Wistar rat model. Sleep–wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1–21 on pups born to REM sleep‐deprived dams and control rats. Pups of REM sleep‐deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15–21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep–wake cycles, indicated maturational delay in the sleep–wake neural networks. The disruption of time‐bound growth of sleep–wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep–wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep–wake profile in the offspring.     

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1–79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average inter-scorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89–96% for NREM sleep and 54–67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.     

Adrenocorticotropic hormone in the control of renal tubular hydrogen ion secretion. Balance of non-metabolizable base in ACTH-stimulated weanling rats subject to acid or base loading

Groups of weanling rats subject to ACTH-stimulation (tetracosactrin, 1 mg kg-1 day-1) were exposed to heavy oral loads of ammonium chloride (approx. 21 mmol kg-1 day-1) or sodium bicarbonate (approx. 40 mmol kg-1 day-1) for 8 days. During loading with sodium bicarbonate, the animals maintained a normal positive external (whole body) balance of non-metabolizable base (NB), excess NB being excreted quantitatively in the urine, whereas loading with ammonium chloride caused a fall in the mean balance of NB from a reference value of 12.1 mmol per 8 days to about zero. However, in the two groups the concentration in plasma of NB rose from the reference value (41 mmol l-1) to the same level (57 and 59 mmol l-1, respectively; P greater than 0.5) despite extreme differences in rates of gastrointestinal NB absorption, despite a significant rise in the rate of endogenous sulphuric acid production and despite the presence of ample chloride in diet and urine. These results indicate that ACTH determines the extracellular concentration of NB at which exchange of NB takes place by influencing, directly or indirectly, the relative rates of renal tubular H- secretion and Cl- reabsorption at any given rate of tubular reabsorption of Na-. Some cybernetic considerations of the disturbance are presented.     

Sleep deprivation decreases mu and delta opioid receptor binding in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was antagonized by the administration of the opioid receptor antagonist naloxone and increased by opioid agonists. In this paper we show that concomitantly with this behavior, a decreased Bmax of mu and delta opioid receptors is present in the limbic system of these animals. These data suggest an active role of limbic mu and delta receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.     

Effects of indole-pyruvic acid on sleep and food intake in the rat

Indole-pyruvic acid was studied for its short- and long-term effects on electroencephalographic sleep and on food intake in rats implanted with cortical and muscular electrodes. Following a single injection, indole-pyruvic acid (10-50 mg kg-1 i.p.) reduced by 16-23 min (range) the latency of the first slow-wave episode in a dose-related fashion and produced a significant increase in slow-wave sleep time (12-40%) in doses of 10-30 mg kg-1. Rapid eye movement sleep latency and rapid eye movement sleep time were increased (by 23-37 min) and reduced (57-71%) respectively. The effects of indole-pyruvic acid on slow-wave sleep time were still present after 3, 7 and 14 days of chronic administration (10 mg kg-1 day-1), whereas tolerance to the effect of indole-pyruvic acid on rapid eye movement sleep was observed. Daily food consumption was reduced (20-28%) by acute administration of indole-pyruvic acid (15-30 mg kg-1 i.p.), but tolerance developed after 5 days of repeated injections. These findings are in accordance with previous evidence suggesting that indole-pyruvic acid effects may be related to the activation of central serotonin neurons, which are involved in the inhibitory control of sleep and food intake.     

Spontaneous motor activity in the perinatal infant before and after birth: stability in individual differences.

This study was undertaken to determine if a relationship existed between the duration of spontaneous general movements before and after birth. Twenty-two infants were examined three times as fetuses between 38 and 40 weeks gestational age and three times as neonates between 2 and 4 weeks postnatal age. Motor activity level during active sleep periods was quantified by direct sonographic visualization for fetuses and by videotaped images of trunk movement for neonates. We found that both fetuses and neonates exhibited stable individual differences in motor activity level. In addition, infants who moved at a certain rate as fetuses generally moved at the same relative rate as neonates up to 4-weeks postnatal age. Our findings suggested that individual differences in motor activity level in the 1st month following birth probably arise during fetal life.     

Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement

SUMMARY  Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS-2 increase in rats. The waking increase was not blocked by the 5-HT₂ antagonist ritanserin nor by the putative 5-HT_1A antagonist (-)-alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS-2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.     

Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rats displayed particular behaviour characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behaviour was potently antagonized by the administration of the D1-selective antagonist SCH 23390. In this paper we show that concomitantly to this behaviour, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. These data suggest an active role of limbic D1 receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.     

Effect of whisker removal on defensive behavior in rats during early ontogenesis

The effects of restriction of sensory afferentation in rats by vibrissectomy performed daily on days 9 to 20 of life on the formation of defensive reactions in early postnatal ontogenesis were studied. Vibrissectomized and control rat pups were assessed in terms of the extent of motor defensive reactions in response to touching the skin from days 10 to 18 of life, the duration of the freezing reaction at age 20 days, and behavior in the open field at age 25 days. Vibrissectomized rat pups showed the following significant differences from controls: a decrease in the extent of early withdrawal from a potentially dangerous stimulus (at age 12 and 13 days), a decrease in the duration of the freezing reaction, and decreases in that extents of the flight reaction and emotional reactivity in the open field test. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 55, No. 5, pp. 677–683, September–October, 2005.     

The relationship between EEG delta activity and autonomic activity as measured by SCSB during daytime sleep

SUMMARY  The aim of the present work was to study the applicability of the static-charge-sensitive bed (SCSB) method to sleep studies, by comparing autonomic nervous activity measured with the SCSB and EEG delta activity (0.5–2 Hz). Simultaneous polygraphic and SCSB measurements of the first sleep cycle (110 min) were recorded from seven subjects. The amount of delta activity filtered from the EEG was compared in 3 min epochs to an autonomic activity index (AAI) based on cardiac, respiratory and body movement activity.
Individual Spearman rank order correlation coefficients between delta amplitude and the AAI varied from 0.17 to -0.60. Therefore, it is concluded that the relationship between the delta activity and the AAI is not systematic enough for defining 'depth' of sleep at any point in time by using the AAI. However, on average, the SCSB differentiates high and low delta values quite well. With some further improvement of the scoring system the SCSB is a useful tool in comparative sleep studies.     

Emotion and movement: activation of defensive circuitry alters the magnitude of a sustained muscle contraction

Understanding the emotion-movement relationship is crucial to the development of motor theory and movement rehabilitation recommendations for a wide range of diseases and injuries that involve motor impairment. Behaviorally, when movements are executed following exposure to emotional stimuli, evidence suggests that active defensive circuitry results in faster but more variable voluntary movements. However, each of the existing protocols has involved movement execution following the offset of anxiety or emotion eliciting stimuli. The specific aim of this study, therefore, was to determine whether the continued exposure to emotional stimuli would alter the magnitude and variability of a sustained motor contraction. During the presentation of pleasant, unpleasant, neutral, and blank images, participants (N=45) were instructed to respond to the onset of an auditory stimulus by initiating and then sustaining a maximal bimanual isometric contraction of the wrist and finger extensor muscles against two independent load cells (left/right limb). Corroborating previous evidence and supporting hypothesis 1, findings indicated that exposure to unpleasant images lead to an increase in mean force production. Variability of movement, however, did not vary as a function of affective context. These findings indicate that continued exposure to unpleasant stimuli magnifies the force production of a sustained voluntary movement, without sacrificing the variability of that contraction. Mechanism driven open and closed loop explanations are offered for these phenomena, implications are addressed, and future directions are discussed.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

Clomipramine suppresses postnatal REM sleep without increasing wakefulness: implications for the production of depressive behaviors

Clomipramine (CLI), a REM sleep suppressant, alleviates symptoms of depression in adults but produces depressive behaviors if applied neonatally. Both effects of CLI as applied to adults and to neonates have been interpreted as consequences of its involvement in REM sleep deprivation. However, the paradox of these conflicting effects remains to be understood. The current study attempts to find the possible answer by studying the effects of CLI on postnatal sleep. Eight postnatal rats were evaluated polysomnographically for nine days. Four rats were treated with CLI, 40 mg/kg/day for six days, and four rats were treated with equivolume saline during the same period. The results showed that 1) CLI treatment did not reduce the time of phasic muscle activity which appears during slow wave EEG as it did during REM sleep; 2) during treatment, rats treated with CLI had 44.66%-68.62% REM sleep reduction, varied according to age; 3) REM sleep reduction during treatment was generally compensated by non-REM sleep, so that total sleep (and wakefulness) was comparable to that experienced by rats treated with saline; 4) an obvious REM sleep rebound was observed after drug withdrawal at the age of P19. These results suggest that 1) the stage that shows phasic muscle activity simultaneously with a high amplitude EEG is not REM sleep and is likely to be independent from non-REM sleep in terms of the percentile change; 2) REM sleep reduction without a corresponding increase in wakefulness in postnatal rats is likely the mediator of postnatal RSD in the production of adult depression; and 3) the neuronal bases responsible for REM rebound function by the end of the postnatal third week.     

Developmental aspects of 2-way shuttlebox avoidance in the spontaneously hypertensive and normotensive rat

In Experiment I, male and female rats from the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKYN) normotensive strains were given 1 session of 2-way shuttlebox avoidance training at 25–26, 35–36, or 45–46 days of age. The avoidance training was preceded by a pretest which consisted of 10 presentations of the compound conditioned stimulus alone in order to assess any differential tendency of the 2 strains to respond to the presentation of novel stimuli. The WKYN rats made a significantly higher number of pretest avoidance responses and achieved a higher level of avoidance performance than SHR rats. In addition, during the pretest, WKYN rats were more active and had a shorter 1st trial latency. In Experiment II, the pretest phase was replicated with a manipulation of the intensity of the auditory cue. Although the WKYN rats had a higher rate of pretest avoidance than SHR rats, the rate of pretest avoidances increased with intensity in both strains. The WKYN rats had a shorter 1st trial latency and a shorter median latency for the 10 trials and were more active than SHR rats during the pretest. These results relate to age-independent behavioral characteristics of these strains and the question of reactivity to environmental stimulation.     

Development of motor activity in kittens

Developmental alterations in motor activity were quantified for the 1st 7 postnatal months in the kitten. Motor activity measured with a stabilimeter was low and constant for the 1st 9 postnatal days, increased markedly until Day 14, and remained stable until Day 21. Locomotor activity measured in an open field decreased slightly during the 1st 3 weeks, increased markedly during the next 2 weeks, and then remained relatively constant until the 9th week. Activity increased again during the 3rd and 4th month and then declined until 7 months of age. We suggest that the marked increase in motor activity during the 2nd week reflects development of visual and auditory systems whereas the increase in locomotor activity during the 4th and 5th weeks represents maturation of neural systems concerned with motor control. The underlying causes of the final activity changes probably represent the maturation of many neural systems and concomitant development of adult behavior in the cat.     

Stability of motor OR and heart rate habituation rates of infancy

The stability of the OR habituation rate as an individual difference trait was investigated in 2 studies. The 1st focused on motor OR's to auditory stimuli at 3 ages within the 1st month of life, and the 2nd examined the HR responses to auditory stimuli at 4 and 8 months. The results indicate that motor OR's did not differ significantly with age and were moderately stable across ages. The stability decreased with age across consecutive days but increased across consecutive weeks. The cross-age correlation for HR responses was moderate. The results were compared with similar findings on other parameters of the OR.     

Postnatal appearance of 5-HT2A receptors on fast flexor and slow extensor rat motor neurons

Motor neurons to the slowly contracting extensor soleus muscle in behaving rats begin to fire tonically in the 2nd week after birth. In the adult, tonic firing becomes predominant and appears to arise from plateau potentials under monoaminergic control. In the present work, motor neurons to slowly contracting extensor soleus and rapidly contracting extensor digitorum longus, a physiological flexor muscle, were retrogradely labeled with fluorescent dextran and examined for immunoreactivity to 5-HT(2A) receptors in 1 and 2 week old and adult rats. No reactivity was detected at 1 week. At 2 weeks, reactivity was detected on 67% slowly contracting extensor soleus (16 of 24) and 19% extensor digitorum longus (11 of 57) motor neurons. In the adult, the intensity of staining was higher and the percentage of labeled motor neurons 79 for slowly contracting extensor soleus (34 of 43) and 31 for extensor digitorum longus (11 of 35). On slowly contracting extensor soleus motor neurons, labeling appeared more often on soma and dendrites than on dendrites only, whereas on extensor digitorum longus motor neurons, labeling appeared more often on dendrites only. These results are consistent with the hypothesis that serotonergic innervation contributes to the appearance and subsequent increase in tonic firing of rat slowly contracting extensor soleus motor neurons in postnatal development.     

Developmental delays in offspring of rats undernourished or zinc deprived during lactation

Offspring of rats who were zinc or calorie deprived during lactation were administered a battery of reflex and motor tests from postnatal Day 4 to Day 21. Compared to offspring of ad lib-fed control rats, both zinc deprived and undernourished offspring exhibited developmental delays in reflexes which appeared after the first postnatal week (auditory startle, air righting, and rope descent). As the deficiencies continued the delays appeared to be more pronounced. The zinc deficiency did not add to the deficits associated with calorie restriction alone because there were no significant differences between the zinc deficient and undernourished pups on any of the measures except eye opening. When rehabilitated offspring were tested at 45 and 60 days of age for motor deficits there were no significant impairments resulting from preweaning dietary conditions. However, the growth retardation of zinc deprived and undernourished rats persisted long after dietary rehabilitation was implemented.     

The synthesis of glycosaminoglycans in aging rat liver. A brief note

The synthesis of glycosaminoglycans (GAG) was studied in liver slices from postnatal (9 days), young (140 days), adult (490 days) and senescent (940 days) rats. It was found that the rate of synthesis was highest in postnatal rat liver and decreased to about half in young rats with no further reduction in adult and senescent age groups. The specific radioactivity of the precursors of GAG synthesis did not change with age. The synthesis pattern of specific types of GAG in postnatal liver was characterized by a significant higher percentage of chondroitin sulfate and hyaluronic acid. In the following age classes the profile of specific GAG synthesis did not change significantly (heparin sulfate: chondroitin sulfate: hyaluronic acid: “keratin sulfate” = 84%:8.3%:1.5%:1.6%).