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Biomedical subjects

F Obál

Publications and source records attributed to F Obál.

At least 73 records · Page 4Linked to original sources

Structure-activity relationship in the effects of delta-sleep-inducing peptide (DSIP) on rat sleep.

DSIP and its analogues, [D-Trp1]-DSIP, [D-Tyr1]-DSIP, and [D-Trp1]-DSIP1-6, were injected ICV (7 nmol/kg) into rats at dark onset, and the sleep-wake activity was recorded during the 12-hr dark period and the subsequent 12-hr light period. The effects were evaluated with respect to baseline records obtained after artificial CSF injections. DSIP did not increase sleep, whereas both [D-Trp1]-DSIP and [D-Tyr1]-DSIP promoted sleep in the first part of the night. [D-Trp1]-DSIP1-6 had a prompt arousing effect. It is suggested that the sleep-promoting analogues act by facilitating slight endogenous sleep tendencies at some time after dark onset, while DSIP is degraded quickly and is therefore not effective. The increase of W after [D-Trp1]-DSIP1-6 may indicate that DSIP contains a fragment with an arousing effect. The results corroborate the notion that the active DSIP molecule has a pseudo-cyclic structure.

Animals↗

Capsaicin prevents histamine-induced itching.

The effects of topical treatment with capsaicin or mustard oil on histamine-induced pruritus, wheal formation and flare response were studied in the human skin. Capsaicin pretreatment resulted in a reversible marked reduction or abolition of the axon reflex flare, but did not influence whealing. Itching was also strongly diminished or even abolished, provided that the flare response was completely blocked. The onset of itching was significantly promoted by pretreatment of the skin with mustard oil, inducing axon reflex vasodilatation. It is concluded that, in addition to the axon reflex flare, capsaicin-sensitive peptide-containing primary afferent neurones are also intimately involved in the mediation of the sensation of itching.

Administration, Topical↗

Capsaicin impairs preoptic serotonin-sensitive structures mediating hypothermia in rats.

In an attempt to elucidate the possible mechanisms involved in the development of the thermoregulatory disturbances induced by systemic capsaicin treatment, the effects of 5-HT injected into the preoptic region or into the cisterna magna on the body temperature and on tail skin vasodilation were studied in control and capsaicin-treated rats. Intracisternal 5-HT elicited a comparable decrease in body temperature in both groups of animals. In contrast, intrapreoptic injection of different doses of 5-HT-induced tail skin vasodilation and hypothermia in the controls, but not in the capsaicin-treated rats. It is suggested that changes in the sensitivity of preoptic warm-responsive structures to 5-HT may contribute essentially to the specific thermoregulatory impairment brought about by systemic capsaicin treatment.

Animals↗

Changes in the brain and core temperatures in relation to the various arousal states in rats in the light and dark periods of the day.

In rats, brain temperature (Tbr) and core temperature (Tc) were recorded in parallel with the sleep-wake activity throughout the 24-h diurnal cycle, consisting of a 12-h light (L) and a 12-h dark (D) period. In order to characterize the temperature changes associated with the arousal states in the L and the D separately, (i) the average temperatures in wakefulness (W), non-rapid eye movement sleep (NREMS) and REM sleep (REMS), and at the transitions between the arousal states were calculated; (ii) the courses of temperatures before and after the transitions (falling asleep, awakening from NREMS or REMS, transition from NREMS to REMS) were determined; (iii) the rates of changes in Tbr and Tc were calculated for each state; and (iv) the correlations between the temperatures and the overall length of each arousal state, and between Tbr and Tc were studied. In both the L and D periods, Tbr and Tc decreased at the beginning of NREMS, then levelled off, and increased slightly before awakening. Apart from short arousals which did not affect temperature, Tbr and Tc increased in W, peaked 15-20 min after awakening, and declined significantly before the falling asleep. In REMS, Tbr increased at a high rate, while a slight increase in Tc was evident in the L only. Correlations between the temperatures and the arousal states were found in both the L and the D. The courses of Tbr and Tc were also correlated. The results support the existence of characteristic changes in body temperature related to the arousal states in the rat.

Animals↗

Effects of acute and chronic treatment with amitryptyline on the sleep-wake activity of rats.

Amitriptyline (1, 5 or 15 mg/kg intraperitoneally, twice a day) was administered to rats and the sleep-wake activity was recorded for either 24 hr (1 mg/kg) or 12 hr (5 or 15 mg/kg) on the day before treatment with amitriptyline, on days 1 and 5 of the treatment and on day 6, when the drug was withdrawn. In the first 3 hr amitriptyline increased non-REM sleep (NREMS), and decreased REM sleep (REMS) and wakefulness; the effects were dose-dependent. The changes in non-REM sleep and wakefulness (W) were followed by a compensatory reaction 6-12 hr after the treatment. The effects of chronic injection of amitriptyline on non-REM sleep revealed a definite decrease only in the case of the 15 mg/kg dose. Rebound of REM sleep appeared after withdrawal of the 5 and 15 mg/kg doses. Amitriptyline at 1 mg/kg had no effect on the sleep-wake activity during the dark period. The results show that the increase in non-REM sleep is as characteristic of amitriptyline as the reduction of REM sleep, and that these effects are resistant to chronic treatment when the dose is small.

Amitriptyline↗

Effects of intracerebroventricular injection of delta sleep-inducing peptide (DSIP) and an analogue on sleep and brain temperature in rats at night.

The effects of ICV injections of DSIP and omega-amino-caprilyl-DSIP (C-DSIP) on the sleep-wake activity and brain temperature (Tbr were studied in rats. The substances (7 nmol/kg) were injected at dark onset, and the sleep-wake activity and Tbr were recorded for 24 hr (dark and light periods, 12 hr each). Relative to the control recordings obtained after artificial CSF injection, the duration of sleep did not increase after either DSIP or C-DSIP. The only significant reaction was an increase of W 6 to 9 hr after the injection of either peptide. The course of Tbr after DSIP and C-DSIP was also identical to that recorded after the injection of artificial CSF. It seems that DSIP administered in a single ICV injection at dark onset does not promote sleep. The increase in W might be attributed to an indirect effect of DSIP or to a degradation product of the peptide.

Animals↗

The modulation of cutaneous inflammatory reactions by peptide-containing sensory nerves.

In the present experiments the role of unmyelinated sensory fibres in the mechanism of cutaneous inflammatory reactions under normal and pathological conditions has been studied in man and animals. Dye leakage responses to histamine, serotonin, compound 48/80, bradykinin and substance P were significantly reduced, while neurogenic inflammation was completely abolished in rats treated neonatally with capsaicin, as studied quantitatively by the Evans blue technique. Neurogenic inflammation could also be elicited by mustard oil in normally innervated human skin, but not in skin areas affected by herpes zoster or in a patient suffering from congenital analgesia. Repeated topical treatment of the skin with capsaicin (local desensitization) abolished the neurogenic inflammatory response for several days. Chemical pain sensitivity was strongly reduced, and thresholds for warmth and heat pain sensations were significantly elevated. Local capsaicin desensitization of the skin prevented whealing, flare and itch in patients with acquired cold and heat urticaria. The findings indicate that peptide-containing sensory nerves are involved in the mediation of chemogenic and heat pain, and possibly itch, and are responsible for initiation of the neurogenic inflammatory response. The results also provide direct evidence of the involvement of these particular sensory nerves in the modulation of the permeability-increasing effects of putative mediators of acute inflammatory reactions. It is concluded that, through modulation of cutaneous vascular reactions, peptidergic sensory nerves may play a hitherto unrecognized role in the pathomechanism of certain diseases of human skin.

Animals↗

The capsaicin sensitivity of the preoptic region is preserved in adult rats pretreated as neonates, but lost in rats pretreated as adults.

Two days old rats were pretreated with subcutaneous injection of 50 mg/kg, and adult animals with either 20, 50 or 300 mg/kg capsaicin. The responsiveness of these and naive animals to microinjection into the preoptic region of capsaicin (10 micrograms) and to subcutaneously injected capsaicin (2 mg/kg) was studied at the age of 3--4 months by recording the tail skin vasodilatation and colon temperature, respectively. On preoptic injection of capsaicin, the reaction of neonatally-pretreated adult rats was similar to that of naive animals, while in all groups pretreated as adults the tail skin vasodilatation was abolished. In response to 2 mg/kg capsaicin administered subcutaneously, the group pretreated neonatally and the adults pretreated with 20 mg/kg capsaicin produced significantly less hypothermia than the naive animals. Rats pretreated as adults with 50 and 300 mg/kg capsaicin failed to show a hypothermic reaction. It is concluded that the sensitivity of the preoptic region to capsaicin is preserved when 2 days old rats are treated with the drug, but lost when adults are injected with capsaicin. These features of capsaicin sensitivity indicate a functioning preoptic and an impaired extrapreoptic thermoregulation in rats pretreated with capsaicin as neonates.

Age Factors↗

Impaired thermoregulation against cold in capsaicin pretreated rats.

A study was made of the effects of pretreatment with fractionated capsaicin on the changes in body temperature (Tb) induced in rats by exposure to cold and to warm environments, and by administration of histamine (40 mg X kg-1) or of pentobarbital (20 mg X kg-1). At the ambient temperature of 22 degrees C the Tb of capsaicin pretreated rats was lower than that of rats treated only with solvent (p less than 0.001). The capsaicin pretreated rats showed impairment of thermoregulation at both high and low environmental temperatures: their Tb rose to a higher level in a warm environment, while in a cold environment their Tb was lower than that of the control rats. Histamine and pentobarbital caused larger drops in the Tb of capsaicin pretreated rats than in the controls. These findings challenge the concept that capsaicin treatment acts exclusively on thermoregulatory mechanisms concerned with warmth sensation.

Animals↗

Morphine tolerance and withdrawal in capsaicin--pretreated rats.

Thermoregulatory reactions to warm exposure and naloxone treatment, as well as behavioral reactions to morphine withdrawal, were recorded in morphine tolerant rats after capsaicin pretreatment. Enhanced behavioural reactions to morphine withdrawal were found in capsaicin pretreated rats, although no differences in degree of withdrawal hypothermia were seen. Morphine tolerant rats displayed increased thermal tolerance; this was partially prevented by capsaicin pretreatment. The results provide further evidence concerning the interference of neural mechanisms sensitive to capsaicin and opiates.

Animals↗

Stress-related changes of opiate sensitivity in thermoregulation.

Body temperature reactions to morphine were tested in freely-moving adult rats reared without any previous experience to human handling. These animals reacted to 8 mg/kg morphine s.c. with a biphasic hypo-hyperthermic response. When the rats had been handled for six days, the same dose of morphine induced a monophasic hyperthermic reaction. The results are regarded as evidence that stress-related factors interfere with the thermoregulatory effects of morphine.

Animals↗

Effect of ambient temperature on the 24-hour sleep-wake cycle in normal and capsaicin-treated rats.

The 24-hour sleep-wake cycle of untreated, normal rats and of capsaicin-treated rats was continuously recorded by telemetry. Recordings were made on two baseline days at 22 degrees C, two days at 29 degrees C, and two final days at 22 degrees C. In untreated animals the daily amount of waking was reduced by the elevated ambient temperature and nonREM sleep was enhanced. This effect was mainly due to the frequent interruption of the dark-time waking episodes by sleep. In capsaicin-treated animals, raising the ambient temperature did not significantly enhance sleep. However, in both groups of rats the slow wave sleep (SWS) fraction of nonREM sleep was increased after elevating the temperature to 29 degrees C. REM sleep showed a minor increase which was significant only for the capsaicin-treated group. The results suggest that a moderate increase of ambient temperature has two effects: (1) It causes an enhancement of sleep by a reduction in the duration of waking episodes, an effect that may represent a heat-defense response. The attenuation of this response in capsaicin-treated rats may be a consequence of the impairment of warm-receptors. (2) It favors the occurrence of SWS and REM sleep.

Animals↗

Capsaicin pretreatment interferes with the thermoregulatory effect of morphine.

Body temperature changes after the administration of 8 mg/kg morphine sulphate were studied in freely-moving and restrained rats, which were pretreated with capsaicin (300 mg/kg). Morphine caused a hyperthermic response irrespective of the previous capsaicin treatment in freely-moving rats; the lag time from the application of morphine to the hyperthermic maximum was, however, significantly delayed in capsaicin pretreated rats. A careful habituation to the experimental procedure (including injections, taking temperature, etc.) facilitated the hyperthermic response both in the pretreated and the control groups. Restrained rats typically showed a hypothermic response to the same dose of morphine. The drop of body temperature in habituated animals was significantly larger in the case of capsaicin pretreated rats. This potentiation of the hypothermic effect of morphine can be regarded as the primary site of interaction between capsaicin and morphine. Since capsaicin pretreated rats also showed an exaggerated thermoregulatory response to experimental stress, we conclude that the thermoregulatory effects of morphine and endogenous opiates are facilitated after capsaicin pretreatment.

Animals↗

Involvement of sensory nerve endings in cold and heat urticaria.

The involvement of sensory nerve endings in acquired cold and heat urticaria was studied in 8 patients. After repeated topical application of capsaicin, the skin was tested for whealing with cold and heat stimuli. Capsaicin pretreatment prevented the urticarial responses for 4-7 days. Since capsaicin is known to induce selective impairment of the chemosensitive nerve endings, the results suggest that these nerve fibers may play an important role in acquired cold and heat urticaria. The possible mechanisms are discussed.

Adult↗

Dose-response relationships in the thermoregulatory effects of capsaicin.

The hypothermic effect of capsaicin, the reduced responsiveness towards the hypothermic effect of the drug as well as the impairment of thermoregulation in the warm environment subsequent to the administration of different doses of capsaicin have been studies in rats. The mortality after capsaicin treatment has also been established. 1. Capsaicin given subcutaneously in doses of 1-10 mg/kg induced a dose-dependent fall in body temperature lasting for 2-5 h. A single dose of 10 mg/kg caused the most pronounced hypothermic effect reaching its maximum (3,4 degrees C) after 107 min. After higher doses (20-50 mg/kg) the fall in body temperature was less, being similar to that observed after the administration of 1-2 mg/kg. 2. A decreased sensitivity towards the hypothermic effect of a test dose of 2 mg/kg capsaicin, as well as an impaired tolerance to high ambient temperature have been found in rats 2 weeks after the pretreatment either with a single dose of 20-50 mg/kg or fractionated administration of 50 mg/kg capsaicin. The fractionated administration of a dose of 50 mg/kg capsaicin proved to be beneficial in decreasing mortality without affecting the desensitizing effect of capsaicin pretreatment. 3. After single doses of capsaicin the hypothermic period was followed by a dose-dependent hyperthermia which lasted for at least 2 days. A close correlation between the prolonged hyperthermic action and the desensitizing effect of capsaicin administration has also been established. The possible relationship between the desensitizing and hyperthermia inducing effect of capsaicin is briefly discussed.

Animals↗

Elevation of thermoregulatory vasodilatation threshold in the rat after capsaicin treatment.

In control and capsaicin-treated (300 mg/kg) rats tail skin vasodilatation was studied while the body temperature was raised to 38 degrees C, 39 degrees C or 40 degrees C and held at these levels. In the capsaicin-treated rats, at 38 degrees C vasodilatation was weaker than in the controls but at temperatures of 39 degrees C and 40 degrees C a delayed increase in tail vasodilatation occurred to the level observed in the controls. It is concluded that the threshold of vasodilatation response to heat is elevated after capsaicin treatment.

Animals↗