Biomedical subjects

F Obál

Publications and source records attributed to F Obál.

At least 55 records · Page 3Linked to original sources

PubMed1991

Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat.

To study the possible involvement of hypothalamic growth hormone-releasing factor (GRF) in sleep regulation, a competitive GRF-antagonist, the peptide (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2, was intracerebroventricularly injected into rats (0.003, 0.3, and 14 nmol), and the EEG and brain temperature were recorded for 12 h during the light cycle of the day. Growth hormone (GH) concentrations were determined from plasma samples taken at 20-min intervals for 3 h after 14 nmol GRF-antagonist. The onset of non-rapid eye movement sleep (NREMS) was delayed in response to 0.3 and 14 nmol GRF-antagonist, the duration of NREMS was decreased for one or more hours and after 14 nmol EEG slow wave amplitudes were decreased during NREMS in postinjection hour 1. The high dose of GRF-antagonist also suppressed REMS for 4 h, inhibited GH secretion, and elicited a slight biphasic variation in brain temperature. These findings, together with previous observations indicating a sleep-promoting effect for GRF, support the hypothesis that hypothalamic GRF is involved in sleep regulation and might be responsible for the correlation between NREMS and GH secretion reported in various species.

Animals↗

PubMed1991

Ruthenium red inhibits tail skin vasodilatation evoked by intracerebroventricular injection of capsaicin in the rat.

The effect of Ruthenium red on the tail skin vasodilatation evoked by an intracerebroventricular injection of capsaicin was studied in the anesthetized rat. Injection of capsaicin into the lateral ventricle resulted in a marked elevation of the tail skin temperature, indicative of peripheral vasodilatation. Ruthenium red, given by intracerebroventricular injection, significantly inhibited this response, which is known to be mediated by central warmth-sensitive neuronal structures. The findings suggest that the sensitivity to Ruthenium red, reportedly characteristic of the capsaicin-sensitive neurons in the peripheral nervous system, is also a trait of the capsaicin-sensitive nerve cells in the central nervous system. This is the first evidence indicating that similar molecular mechanisms, presumably involving changes in cellular calcium metabolism, contribute to the capsaicin-induced activation of neurons in both the peripheral and central nervous systems.

Animals↗

PubMed1991

Cholecystokinin promotes sleep and reduces food intake in diabetic rats.

It has been reported that systemic injections of cholecystokinin (CCK) elicit the behavioral characteristics of satiety, including sleep, in rats. CCK is a potent stimulator of insulin secretion, and insulin is hypothesized to be involved in sleep and feeding regulation. The purpose of the current experiments was to study the possible role of endogenous insulin in the food-intake-reducing and hypnogenic effects of intraperitoneally (IP) administered CCK. Normal and streptozotocin (STR)-diabetic rats were injected with isotonic saline or CCK (10 and 50 micrograms/kg) at dark onset, and sleep-wake activity was determined for the next 12 h. There were no significant differences between the baseline sleep-wake activity of normal and diabetic rats. IP injection of CCK elicited a selective increase in nonrapid-eye-movement sleep in both groups during the first postinjection hour. In a separate experiment, the effects of CCK (10 micrograms/kg) on food intake were determined in control and diabetic rats; CCK suppressed the 1-h food intake in both groups. In a third experiment, the effects of CCK treatment (50 micrograms/kg) on plasma insulin levels were determined. In normal rats, CCK elicited a two-fold increase in plasma insulin concentration, whereas diabetic rats had a significantly lower basal insulin level which was not affected by CCK treatment. We conclude that hypnogenic and food-intake-reducing effects of exogenously administered CCK are closely associated; however, pancreatic insulin does not play a significant role in either of these effects.

Animals↗

PubMed1991

Intraperitoneal injection of cholecystokinin elicits sleep in rabbits.

Cholecystokinin (CCK) reduces food intake and promotes non-rapid-eye-movement sleep (NREMS) in rats. The purpose of present experiments was to determine if CCK is somnogenic in rabbits; another species in which CCK suppresses feeding. White New Zealand rabbits were treated intracerebroventricularly (ICV; 0.05, 0.5 and 2 micrograms) or intraperitoneally (IP; 2.5, 10 and 40 micrograms/kg) with CCK or saline, and sleep-wake activity and brain temperature (Tbr) were recorded for 6 h. Injections of 10 and 40 micrograms/kg CCK IP elicited a decrease in wakefulness and an increase in NREMS during the first hour postinjection. The hypnogenic effects were accompanied by a decrease in Tbr. After the IP injection of a lower dose (2.5 micrograms/kg) a slight, nonsignificant increase in NREMS during the first hour postinjection was followed by a decrease in NREMS. ICV injections of CCK had relatively small inhibitory effects on sleep. We conclude that circulating, hormone CCK might be a hypnogenic signal with a peripheral site of action.

Animals↗

PubMed1991

Macrophages produce somnogenic and pyrogenic muramyl peptides during digestion of staphylococci.

Muramyl peptides have a variety of biological effects in mammals, including enhancement of the immune response, sleep, and body temperature. Although mammals lack biosynthetic pathways for muramyl peptides, they are found in mammals and are well known as components of bacterial cell walls. This suggests that phagocytic mammalian cells digest bacterial cell walls and produce biologically active muramyl peptides. Staphylococcal cell walls were radioactively labeled during growth of the bacteria. During the digestion of these radiolabeled bacteria, murine bone marrow macrophages produced low-molecular-weight substances that coeluted chromatographically with the radioactive cell wall marker. Further separation of these substances using reversed-phase high-performance liquid chromatography resulted in the isolation of substances with high specific biological activity. Intracerebroventricular injection of rabbits with these substances induced an increase in slow-wave sleep and body temperature and a suppression of rapid-eye-movement sleep. The characteristics of the biological responses and the chromatographic behavior of the active components are consistent with those of muramyl peptides. The ability of macrophages to tailor muramyl peptides from peptidoglycan may provide an amplification step for the immune response. Muramyl peptides released by macrophages may also act as mediators for various facets of the acute phase response elicited by bacterial infections such as fever and sleep.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Sleep in diabetic rats: effects of interleukin 1.

Previous observations indicate that both interleukin 1 beta (IL-1 beta) and insulin are involved in sleep regulation. IL-1 beta has been reported to stimulate insulin secretion, suggesting that some of the effects of IL-1 beta are mediated by insulin. The purpose of the current experiments was to study the possible role of endogenous insulin in physiological sleep regulation and in the hypnogenic effects of exogenously administered IL-1 beta. Isotonic saline or IL-1 beta (2.5 ng) was intracerebroventricularly injected into normal and streptozocin-diabetic rats at dark onset, and sleep-wake activity and brain temperature were recorded for 24 h. Blood samples were collected every 20 min during the first hour postinjection for plasma insulin measurement. In diabetic rats, rapid-eye-movement (REM) and non-REM sleep were significantly decreased during the second part of the light period on the baseline day. IL-1 beta elicited a biphasic sleep response in both normal and diabetic rats. This initial increase in non-REM sleep during the first 4 h postinjection was followed by significant sleep suppression in both groups. Brain temperature was not affected in either group. Plasma insulin concentration decreased in response to IL-1 beta in normal rats, whereas insulin was below the level of detection in the diabetic rats. These results indicate that, although sleep is disturbed in diabetic rats, pancreatic insulin might not have a decisive role in the regulation of sleep in rats, and it does not mediate the effects of IL-1 beta on sleep-wake activity.

Animals↗

PubMed1991

A possible pathomechanism of the idiopathic cold contact urticaria.

Urtica is characterized by an erythematous wheal surrounded by a flare and is frequently caused by physical agents (e.g. cold). The exact mechanism and mediators involved in the mechanism of physical urticaria are not known. This study of the role of the neurogenic factors in cold urticaria showed, that local capsaicin treatment (desensitization) of the skin in patients with cold urticaria resulted in the abolition of whealing in response to cold. This result suggests that C-fibers might play an important role in the pathomechanism of idiopathic contact cold urticaria.

Adult↗

PubMed1990

Brain and core temperatures and peripheral vasomotion during sleep and wakefulness at various ambient temperatures in the rat.

Changes in brain, core and tail skin temperatures (Tbr, Tc and Tt) associated with transitions in the arousal states were recorded in rats throughout the 24-h diurnal cycle at 10 degrees C, 21 degrees C and 29 degrees C. Falling asleep was accompanied by decreases in both Tbr and Tc and vasodilation at 10 degrees C and 21 degrees C. At 29 degrees C, tail vessels were permanently dilated, and further dilation was not found on sleep onset. Tbr and Tc, however, continued to decrease during non-rapid-eye-movement sleep (NREMS); these changes are likely to result from reductions in heat production and increased conductive heat loss. The changes in Tbr, Tc and Tt on awakening mirrored those on falling asleep. It is suggested that the suppression of sleep in the cold and the enhancement of NREMS in the heat promote thermoregulation. Rapid-eye-movement sleep (REMS) was associated with sharp rises in Tbr. The rise in Tbr was the largest in the cold and was attenuated at 29 degrees C. Tc decreased and Tt increased in the cold, whereas Tc tended to increase and Tt to decrease in the heat. The paradoxical peripheral vasomotion during REMS supports previous suggestions on severe thermoregulatory impairment during REMS in other species.

Animals↗

PubMed1989

Corticotropin-releasing factor attenuates interleukin 1-induced sleep and fever in rabbits.

Interleukin 1 (IL-1), a key mediator of the acute phase response, stimulates hypothalamic corticotropin-releasing factor (CRF) release. The CRF-adrenocorticotrophic hormone (ACTH)-glucocorticoid axis is a feedback for peripheral production and action of IL-1. Effects of intracerebroventricularly administered CRF on rabbit sleepwake activity, brain temperature (Tbr), and behavior and on the central effects of IL-1 [fever and excess non-rapid-eye-movement sleep (NREMS)] were studied. CRF (0.1-1.25 micrograms) dose dependently decreased NREMS and enhanced wakefulness. IL-1-induced excess NREMS was inhibited by CRF. Rapid-eye-movement sleep (REMS) suppressed by IL-1 was partially restored by 0.1 or 0.5 microgram CRF, although CRF itself did not promote REMS. Behavioral effects of intracerebroventricular CRF were relatively small, although 1.25 micrograms abolished ingestion for 3 h, suppressed rearing behavior, and increased sitting behavior. Tbr increased after CRF injection alone. After IL-1 pretreatment, however, 0.1 and 0.5, but not 1.25, micrograms CRF reduced IL-1-induced fever after several hours. These results implicate IL-1-induced CRF release as part of a negative-feedback mechanism attenuating not only peripheral IL-1 actions but also its central effects.

Animals↗

PubMed1988

Effects of nocturnal intraperitoneal administration of cholecystokinin in rats: simultaneous increase in sleep, increase in EEG slow-wave activity, reduction of motor activity, suppression of eating, and decrease in brain temperature.

Rats received an i.p. injection of cholecystokinin-octapeptide sulfate ester (CCK; 4, 10 or 50 micrograms/kg) or physiological saline at dark onset, and the 24-h sleep-wake cycle (12-h-dark and 12-h-light phases), spontaneous motor activity and brain temperature (Tbr) were recorded. EEG activity was studied through spectral analysis for 2.5 h, and food intake was measured at the end of postinjection hour 1. In response to CCK, non-REM sleep increased at the expense of wakefulness, and the sleep-promoting effect was substantiated by an increase in EEG slow-wave activity. Motor activity, Tbr and food intake decreased. The effects vanished in postinjection hour 2; the diurnal rhythms were not modified. The changes varied as a function of the dose: the effects were significant following 10 micrograms/kg, and even higher in response to 50 micrograms/kg CCK. The results indicate that i.p. CCK definitely promotes non-REM sleep. This effect may belong to the behavioral sequence elicited by the peptide, which is often attributed to satiety. As evidenced by the reduction of Tbr, CCK also exerts strong autonomic actions, which might interfere with the behavioral responses.

Animals↗

PubMed1988

Effects of alpha-MSH on sleep, behavior, and brain temperature: interactions with IL 1.

Changes in rabbit sleep-wake activity, brain temperature (Tbr), and behavior were studied after intracerebroventricular injections of a putative endogenous antipyretic, alpha-melanocyte-stimulating hormone (alpha-MSH), and of an endogenous pyrogen, interleukin 1 (IL 1-beta). alpha-MSH (0.1-50.0 micrograms) dose dependently increased wakefulness (W) and decreased Tbr, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). NREMS was more sensitive than REMS to the suppressive effects of low alpha-MSH doses. EEG slow-wave activity in NREMS decreased after alpha-MSH treatment. alpha-MSH elicited stretching, yawning, and signs of sexual excitation. IL 1 (20 and 40 ng) induced fever and excess NREMS. alpha-MSH administered 30 min after IL 1 (40 or 20 ng IL 1 + 0.1, 0.5, or 5.0 micrograms alpha-MSH) significantly attenuated IL 1-induced fever and excess NREMS. IL 1 failed to alter the behavioral effects of alpha-MSH. Despite alpha-MSHs effect on rabbit behavior, total motor activity time did not increase, indicating that increased W after alpha-MSH cannot be attributed to behavioral activation. These results suggest that, besides acting as an endogenous antipyretic, alpha-MSH might be involved in regulation of IL 1-induced sleep.

Animals↗

PubMed1987

Effects of acute and chronic treatment with an atypical antidepressant drug, nomifensine, on the sleep-wake activity in rats.

After the chronic administration of saline, rats were treated with nomifensine (0.1 or 1.0 mg/kg, twice a day, at light and dark onset) for 11 days. The sleep-wake activity was recorded for 24 h on the baseline day (saline), on nomifensine days 1, 5 and 11, and also on day 12, when saline was injected again (withdrawal day). Another group of rats was treated with saline throughout the experiment, without significant effect on the sleep-wake activity. The smaller dose of nomifensine increased non-REM sleep (NREMS) at the expense of wakefulness (W) in the light period. The effect persisted throughout the chronic treatment. A late increase in REM sleep (REMS) was noted on nomifensine days 5 and 11. Nomifensine failed to affect the sleep-wake activity in the dark period. On withdrawal, the baseline percentages of the vigilance states were recovered. As evaluated through spectral analysis of the EEG, the increase in NREMS was accompanied by an increase in slow wave activity. The higher dose of nomifensine elicited an increase in W and a reduction in both sleep states, followed by changes in W and NREMS in the opposite directions. These effects were evident in both the light and the dark periods of the day. Chronic treatment resulted in circadian variations in the effects. Withdrawal of the drug abolished the arousal reaction, but the late increase in NREMS persisted. The dose-dependent biphasic effects of nomifensine on sleep-wake activity can be explained by considering the proposed indirect dopamine and possibly noradrenaline agonist activity of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Dopamine autoreceptor antagonists: effects on sleep-wake activity in the rat.

The effects of the putative dopamine (DA) autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, and cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, on sleep-wake activity, EEG, and motor activity in the rat were studied. Both drugs induced a dose-dependent increase in wakefulness (W) and a reduction in non-REM sleep (NREMS). A definite tendency to a suppression of REM sleep (REMS) could also be observed. The results of spectral analysis indicated that EEG slow wave activity, a marker of sleep intensity, was particularly sensitive to the drugs. Slight differences between the two drugs were observed: (+)-AJ 76 seemed to be more efficacious than (+)-UH 232 in stimulating motor activity. (+)-UH 232 tended to suppress slow wave activity more strongly than (+)-AJ 76. It is suggested that the increase in W following administration of (+)-AJ 76 resulted predominantly from locomotor activation, while (+)-UH 232 might also act on dopaminergic mechanisms involved in the regulation of sleep.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1987

Indomethacin is effective against neurogenic hyperthermia following cranial trauma or brain surgery.

The effectiveness of indomethacin treatment (1 mg/kg) as an antipyretic was tested in patients after cranial trauma or brain surgery involving the centromedial forebrain. Indomethacin was effective in reducing temperature in 10 of 11 cases which showed a dipyrone-resistant hyperthermia developing in the first 24 hours after brain damage, while no significant antipyretic effect was seen in hyperthermic cases developing more than 72 hours after cranial trauma or brain surgery. Biochemical tests estimating the effect of indomethacin, and pyrazolone derivatives on the arachidonic acid metabolism showed significant effects of indomethacin only in influencing cyclooxygenase activity and no effect of any drugs on lipoxygenase actions. In view of these observations, the use of indomethacin is recommended as a treatment for neurogenic hyperthermia.

Body Temperature↗

PubMed1987

Differences in the mechanisms of the thermoregulatory impairment induced by capsaicin in newborn and adult rats.

The function of heat defence was compared in rats pretreated as adults (A-rats) and neonates (N-rats) with capsaicin. The thermoregulatory impairment as tested by whole body heating was similar in A-rats and N-rats. The thermosensitivity and chemosensitivity of the preoptic region (RPO) seemed to be normal in N-rats. A deficiency of RPO mechanisms could be demonstrated in A-rats. It is suggested that the preoptic effects of capsaicin have but a minor significance for the thermoregulatory impairment. It seems that the main cause of decreased heat tolerance is a reduction of peripheral warm sensation due to degeneration of unmyelinated C-fibre primary neurons in both A-rats and N-rats. The results do not support the primary importance of preoptic warm sensation in physiological thermoregulation.

Animals↗

PubMed1986

Capsaicin pretreatment reduces the gastric acid secretion elicited by histamine but does not affect the responses to carbachol and pentagastrin.

Gastric acid secretion was studied following stimulation with a subcutaneous injection of histamine (0.1, 0.5 or 5 mg/kg), carbachol (4, 40 or 160 micrograms/kg) or pentagastrin (25 or 250 micrograms/kg) in conscious rats pretreated with either capsaicin or the vehicle. The secretory response to histamine (0.5 or 5 mg/kg) was greatly reduced in the capsaicin-treated rats, while the slight effect of 0.1 mg/kg histamine and the increase of secretion in response to carbachol and pentagastrin were not affected. The basal secretion was also normal in the capsaicin-treated rats. It is suggested that unlike the effects of carbachol and pentagastrin, the increase of acid secretion elicited by histamine involves a capsaicin-sensitive mechanism. Since capsaicin is a specific neurotoxin for the peptide-containing primary sensory neurons, the present results may indicate that the neurons contribute essentially to the effect of histamine on gastric acid secretion.

Animals↗

PubMed1986

Vasoactive intestinal polypeptide promotes sleep without effects on brain temperature in rats at night.

The possible sleep-promoting activity of vasoactive intestinal polypeptide (VIP) was contrasted with the physiological sleep suppression in the diurnal active period through the i.c.v. injection of 100 ng VIP into rats at dark onset. The sleep-wake activity and brain temperature (Tbr) were recorded for 24 h (dark period and light period, 12 h each), and the effects were evaluated with respect to records obtained after artificial cerbrospinal fluid injection. Without altering the normal course of Tbr, VIP induced a prompt and persistent increase of sleep. Wakefulness was significantly suppressed and non-REM sleep increased for 6 h, while REM sleep increased for 3 h. The obvious sleep-promoting action of VIP, unrelated to thermoregulatory effects, supports the notion that the peptide might be involved in sleep regulation.

Animals↗

PubMed1986

Effects of capsaicin on central monoaminergic mechanisms in the rat.

The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.

Animals↗