Delayed antihypoxic effect of leu enkephalin in mice

Hypobaric hypoxic hypoxia conditions were simulated by raising mice in the altitude chamber to the level of 10,500-10,700 m. Enkephalin, its analogues, morphine and naloxone were injected once 1, 2, 3, 6 and 14 days prior to the experiment, and then their effects on stability to hypoxia were investigated depending on the time of drug administration. Only leu-enkephalin after a single injection was found to have antihypoxic properties for a week. Naloxone, but not phentolamine hydrochloride, blocked delayed antihypoxic effect of penta-peptide. Leu-enkephalin is thought to be endogenous antihypoxant.     

The effect of ambient temperature on body temperature and on ultrasonic behaviour in litters of albino laboratory mice deprived of their mothers

Litters of mouse pups of various ages when deprived of their mother and kept for one hour at ambient temperatures of 3°C, 12°C and 22°C lose heat less rapidly than pups isolated individually at similar temperatures. The litters are able to maintain constant body temperatures of 35–37°C by day 8 at 22°C, by day 19 at 12°C and by day 21 at 3°C. Very little ultrasound is detected from litters of any age up to 21 days at 22°C while at 12°C ultrasound is mainly detected from pups of 4 and 6 days; very few calls are produced by older pups at this temperature. Considerably more calls are emitted at 3°C than at either of the two higher temperatures. At 3°C the total number of calls emitted during the hour-long exposure period varied markedly with age. There were two peaks of calling, one on day 6 and the other on day 16. The temporal pattern of calling throughout the hour-long exposure period at 3°C was similar in pups of 4 and 6 days and in pups of 8, 10, 12, 14 and 16 days, but differed between these two groups. In the younger group of pups the rate of calling rose to a peak and then decreased to zero as the pups became comatose; in the older pups the rate of calling was low initially then either rose throughout the rest of the hour or rose to a high level that was maintained. It is suggested that the various patterns of ultrasonic calling can be associated with the physiological development of mouse litters.     

The effect of body temperature on the locomotory energetics of lizards

Oxygen consumption (VO2), carbon dioxide production (VCO2), and stamina were measured in the lizard Tupinambis nigropunctatus running at sustainable and non-sustainable velocities (v) on a motor-driven treadmill. Three experimental groups were measured: field-fresh animals at body temperature (Tb) = 35 degrees C and laboratory-maintained animals at Tb = 35 and 25 degrees C. Mean preferred Tb was determined to be 35.2 degrees C. At 35 degrees C, field-fresh animals had a greater maximal oxygen consumption (VO2max corr) (4.22 vs 3.60 ml O2 g-0.76h-1) and a greater endurance. The net cost of transport (slope of VO2 on v) did not differ between the groups (= 2.60 ml O2 g-0.76)km-1). Velocity at which VO2max is attained (MAS) is 0.84 km h-1. The respiratory exchange ratio (R) exceeded 1.0 at v above MAS, indicating supplementary anaerobic metabolism. At 25 degrees C, VO2max corr was lower (2.34 ml O2 g-0.76h-1) as was endurance, MAS occurring at 0.5 km h-1. Net cost of transport was not significantly different than at 35 degrees C. The effect of Tb on locomotory costs was analyzed for this lizard and other species. It was concluded that the net cost of transport is temperature independent in all species examined and the total cost of locomotion (VO2 v-1) is temperature dependent in Tupinambis (Q10 = 1.4-2.0) and all other species examined except one. The energetic cost of locomotion [(VO2active-VO2rest)v-1], previously reported to be temperature independent in lizards, is temperature dependent in Tupinambis (Q10 = 1.3-1.6) and in two other species.2r     

The effect of clenbuterol on body composition in spontaneously eating tumour-bearing mice

The aim of this study was to investigate the effect of a selective ₂-adrenoceptor agonist, clenbuterol, on body composition in tumour-bearing adult and growing mice. Therefore, adult female C57/BL6 mice (n=20) were inoculated subcutaneously with a 3-methylcholanthrene-induced sarcoma and divided into two identical groups. One group received injections twice a day of clenbuterol corresponding to 1 mg/kg body weight, the other group received sham injections. Growing mice (n=20) were similarly divided after tumour inoculation into one study group with clenbuterol injections and one control group. The growing animals were sacrificed on day 11 after commencement of treatment, the adult mice on day 16.Clenbuterol treatment had no statistically significant effect on accumulated food intake or body composition in the adult mice. However, fooe intake in these animals increased numerically compared to control animals after day 12 of the study. Tumour growth was also unaffected. The growing animals displayed an increased carcass dry weight with borderline significance (p=0.06) and an increased quadriceps muscle fat free dry weight after clenbuterol treatment. Tumour growth was not affected. Food intake measured on a daily basis was significantly increased in the growing clenbuterol treated animals and accumulated food intake was increased with a trend towards statistical significance (p=0.06). The results support the suggestion that treatment with a selective ₂-adrenoceptor agonist does not improve body composition in tumour-bearing adult mice relying on spontaneous food intake while growing animals may benefit from such treatment.     

Interaction of dimers of inactive enkephalin fragments with mu opiate receptors

Dimeric analogues of the inactive enkephalin fragment Tyr-D-Ala-Gly were synthesized by cross-linking with alkanediamine at the C-terminus. Biological evaluation of these dimers (H-Tyr-D-Ala-Gly-NH)2.(-CH2-)n (DTREn), where n = 0-6, revealed that the fragment inactive for mu receptors was activated by its dimerization, with the maximum activation found with DTRE2, and that the dimer was highly mu-selective. So-called "handicapped" dimers, which lack one of the essential groupings required for enkephalin activity, were found to be far less active, indicating that the dimer interacts bivalently with mu receptors. It seems, therefore, that mu opiate receptors contain at least two equivalent binding sites which are extremely close to each other.     

The effect of body temperature on the hunting response of the middle finger skin temperature

The relationship between body temperature and the hunting response (intermittent supply of warm blood to cold exposed extremities) was quantified for nine subjects by immersing one hand in 8°C water while their body was either warm, cool or comfortable. Core and skin temperatures were manipulated by exposing the subjects to different ambient temperatures (30, 22, or 15°C), by adjusting their clothing insulation (moderate, light, or none), and by drinking beverages at different temperatures (43, 37 and 0°C). The middle finger temperature (T _fi) response was recorded, together with ear canal (T _ear), rectal (T _re), and mean skin temperature (Tˉ _sk). The induced mean T _ear changes were −0.34 (0.08) and +0.29 (0.03)°C following consumption of the cold and hot beverage, respectively. Tˉ _sk ranged from 26.7 to 34.5°C during the tests. In the warm environment after a hot drink, the initial finger temperature (T _fi,base) was 35.3 (0.4)°C, the minimum finger temperature during immersion (T _fi,min) was 11.3 (0.5)°C, and 2.6 (0.4) hunting waves occurred in the 30-min immersion period. In the neutral condition (thermoneutral room and beverage) T _fi,base was 32.1 (1.0)°C, T _fi,min was 9.6 (0.3)°C, and 1.6 (0.2) waves occurred. In the cold environment after a cold drink, these values were 19.3 (0.9)°C, 8.7 (0.2)°C, and 0.8 (0.2) waves, respectively. A colder body induced a decrease in the magnitude and frequency of the hunting response. The total heat transferred from the hand to the water, as estimated by the area under the middle finger temperature curve, was also dependent upon the induced increase or decrease in T _ear and Tˉ _sk. We conclude that the characteristics of the hunting temperature response curve of the finger are in part determined by core temperature and Tˉ _sk. Both T _fi,min and the maximal finger temperature during immersion were higher when the core temperature was elevated; Tˉ _sk seemed to be an important determinant of the onset time of the cold-induced vasodilation response. Accepted: 29 April 1997     

Decrease of core body temperature in mice by dehydroepiandrosterone

Dietary dehydroepiandrosterone (DHEA) reduces food intake in mice, and this response is under genetic control. Moreover, both food restriction and DHEA can prevent or ameliorate certain diseases and mediate other biological effects. Mice fed DHEA (0.45% w/w of food) and mice pair-fed to these mice (food restricted) for 8 weeks were tested for changes in body temperature. DHEA was more efficient than food restriction alone in causing hypothermia. DHEA injected intraperitoneally also induced hypothermia that reached a nadir at 1 to 2 hr, and slowly recovered by 20 to 24 hr. This effect was dose dependent (0.5-50 mg). Each mouse strain tested (four) was susceptible to this effect, suggesting that the genetics differ for induction of hypophagia and induction of hypothermia. Because serotonin and dopamine can regulate (decrease) body temperature, we treated mice with haloperidol (dopamine receptor antagonist), 5,7-dihydroxytryptamine (serotonin production inhibitor), or ritanserin (serotonin receptor antagonist) prior to injection of DHEA. All of these agents increased rather than decreased the hypothermic effects of DHEA. DHEA metabolites that are proximate (5-androstene-3beta, 17beta-diol and androstenedione) or further downstream (estradiol-17beta) were much less effective than DHEA in inducing hypothermia. However, the DHEA analog, 16alpha-chloroepiandrosterone, was as active as DHEA. Thus, DHEA administered parentally seems to act directly on temperature-regulating sites in the body. These results suggest that DHEA induces hypothermia independent of its ability to cause food restriction, to affect serotonin or dopamine functions, or to act via its downstream steroid metabolites.     

Effects of the enkephalin analogue FK33-824 on rectal temperature and respiratory rate in male mice

Subcutaneous administration of the enkephalin analogue FK33-824 (FK) elicited a dose-related decrease in rectal temperature and respiratory rate in male ddY strain mice. Naloxone and 3 days' implantation of morphine pellet decreased the effects of FK, suggesting the involvement of opioid receptors and cross-tolerance with morphine to both effects of FK. A positive correlation was found between the FK-induced decrease in rectal temperature and that in respiratory rate among the 6 strains of inbred mice including BALB/c, C3H, A/J, CBA, C57BL/6 and DBA/2. The degree of hypothermia elicited by FK was different among strains, whereas marginal strain difference was seen in the respiratory depression induced by FK. The strain difference in the FK responses may be due to the difference in the opioid receptor subtypes in the brain.     

Effects of beta-endorphin on body temperature in mice at different ambient temperatures

The effect of intracerebroventricular injection of beta-endorphin (beta-END) on body temperature of mice was studied at ambient temperatures (Ta) of 10 degrees, 20 degrees and 31 degrees C. Doses between 0.1 and 10.0 microgram/mouse were studied. The lower (less than 1 microgram) doses of beta-END produced a hyperthermia at all Ta's studied. The higher doses of beta-END produced hyper- or hypothermia depending on the Ta. The subcutaneous injection of naloxone (1 mg/kg) antagonized the high dose hypothermic effects, but not the hyperthermic effect of beta-END. These data suggest that there may be different receptors and/or sites of action for high and low doses of beta-END.     

Elevated body temperature during sleep in orexin knockout mice

Core body temperature (Tb) is influenced by many physiological factors, including behavioral state, locomotor activity, and biological rhythms. To determine the relative roles of these factors, we examined Tb in orexin knockout (KO) mice, which have a narcolepsy-like phenotype with severe sleep-wake fragmentation. Because orexin is released during wakefulness and is thought to promote heat production, we hypothesized that orexin KO mice would have lower Tb while awake. Surprisingly, Tb was the same in orexin KO mice and wild-type (WT) littermates during sustained wakefulness. Orexin KO mice had normal diurnal variations in Tb, but the ultradian rhythms of Tb, locomotor activity, and wakefulness were markedly reduced. During the first 15 min of spontaneous sleep, the Tb of WT mice decreased by 1.0 degrees C, but Tb in orexin KO mice decreased only 0.4 degrees C. Even during intense recovery sleep after 8 h of sleep deprivation, the Tb of orexin KO mice remained 0.7 degrees C higher than in WT mice. This blunted fall in Tb during sleep may be due to inadequate activation of heat loss mechanisms or sustained activity in heat-generating systems. These observations reveal an unexpected role for orexin in thermoregulation. In addition, because heat loss is an essential aspect of sleep, the blunted fall in Tb of orexin KO mice may provide an explanation for the fragmented sleep of narcolepsy.     

The effect of enkephalin analogue on pituitary hormone release in human obesity

To elucidate further the role of opioid systems in the neuroendocrine alterations associated with obesity, we investigated the effect of the synthetic enkephalin analogue DAMME in 11 obese subjects and 10 lean controls. Prolactin responses to DAMME were similar in lean and obese, even in those obese subjects who had absent prolactin responses to insulin-induced hypoglycaemia. The obese showed impaired growth hormone release after both DAMME and insulin-induced hypoglycaemia compared to the lean subjects. The discordance of prolactin responses to DAMME and insulin-induced hypoglycaemia in the obese suggests that altered opioid systems are unlikely to account for the hypothalamic dysfunction present in obesity.     

The effect of fast created inbreeding on litter size and body weights in mice

This study was designed to reveal any differences in effects of fast created versus total inbreeding on reproduction and body weights in mice. A line selected for large litter size for 124 generations (H) and a control line (K) maintained without selection for the same number of generations were crossed (HK) and used as a basis for the experiment. Within the HK cross, full sib, cousin or random mating were practised for two generations in order to create new inbreeding (IB_F) at a fast rate. In the first generation of systematic mating, old inbreeding was regenerated in addition to creation of new inbreeding from the mating design giving total inbreeding (IB_T). The number of pups born alive (NBA) and body weights of the animals were then analysed by a model including both IB_T and IB_F. The IB_T of the dam was in the present study found to reduce the mean NBA with -0.48 (± 0.22) (p < 0.05) pups per 10% increase in the inbreeding coefficient, while the additional effect of IB_F was -0.42 (± 0.27). For the trait NBA per female mated, the effect of IB_T was estimated to be -0.45 (± 0.29) per 10% increase in the inbreeding coefficient and the effect of IB_F was -0.90 (± 0.37) (p < 0.05) pups. In the present study, only small or non-significant effects of IB_F of the dam could be found on sex-ratio and body weights at three and six weeks of age in a population already adjusted for IB_T.