Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially

When rats, acclimated to an ambient temperature (T(a)) of 29 degrees C, are exposed to 10% O(2) for 63 h, the circadian rhythms of body temperature (T(b)) and level of activity (L(a)) are abolished, T(b) falls to a hypothermic nadir followed by a climb to a hyperthermic peak, L(a) remains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378-R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of T(a) in these hypoxic-induced responses, T(b) and L(a) data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O(2) from rats acclimated to 25 or 21 degrees C. Magnitudes and rates of decline in T(b) after onset of hypoxia were inversely proportional to T(a), whereas magnitudes and rates of T(b) climb after the hypothermic nadir were directly proportional to T(a). No hyperthermia, so prominent at 29 degrees C, occurred at 25 or 21 degrees C. The hypoxic depression of L(a) was least at 21 degrees C and persisted throughout the hypoxia. In contrast, T(a) was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in T(b). We propose that the absence of hyperthermia at 21 and 25 degrees C as well as a persisting hypothermia may protect the brain from overt pathology.     

Circadian rhythm changes in core temperature over the menstrual cycle: method for noninvasive monitoring

The purpose of this study was to determine whether core temperature (T(c)) telemetry could be used in ambulatory women to track changes in the circadian T(c) rhythm during different phases of the menstrual cycle and, more specifically, to detect impending ovulation. T(c) was measured in four women who ingested a series of disposable temperature sensors. Data were collected each minute for 2-7 days and analyzed in 36-h segments by automated cosinor analysis to determine the mesor (mean temperature), amplitude, period, acrophase (time of peak temperature), and predicted circadian minimum core temperature (T(c-min)) for each cycle. The T(c) mesor was higher (P < or = 0.001) in the luteal (L) phase (37.39 +/-0.13 degrees C) and lower in the preovulatory (P) phase (36.91 +/-0.11 degrees C) compared with the follicular (F) phase (37.08 +/-0.13 degrees C). The predicted T(c-min) was also greater in L (37.06 +/- 0.14 degrees C) than in menses (M; 36.69 +/- 0.13 degrees C), F (36. 6 +/- 0.16 degrees C), and P (36.38 +/- 0.08 degrees C) (P < or = 0. 0001). During P, the predicted T(c-min) was significantly decreased compared with M and F (P < or = 0.0001). The amplitude of the T(c) rhythm was significantly reduced in L compared with all other phases (P < or = 0.005). Neither the period nor acrophase was affected by menstrual cycle phase in ambulatory subjects. The use of an ingestible temperature sensor in conjunction with fast and accurate cosinor analysis provides a noninvasive method to mark menstrual phases, including the critical preovulatory period.     

Exercise delays the hypoxic thermal response in rats.

Exercise exacerbates acute mountain sickness. In infants and small mammals, hypoxia elicits a decrease in body temperature (Tb) [hypoxic thermal response (HTR)], which may protect against hypoxic tissue damage. We postulated that exercise would counteract the HTR and promote hypoxic tissue damage. Tb was measured by telemetry in rats (n = 28) exercising or sedentary in either normoxia or hypoxia (10% O2, 24 h) at 25 degrees C ambient temperature (Ta). After 24 h of normoxia, rats walked at 10 m/min on a treadmill (30 min exercise, 30 min rest) for 6 h followed by 18 h of rest in either hypoxia or normoxia. Exercising normoxic rats increased Tb ( degrees C) vs. baseline (39.68 +/- 0.99 vs. 38.90 +/- 0.95, mean +/- SD, P < 0.05) and vs. sedentary normoxic rats (38.0 +/- 0.09, P < 0.05). Sedentary hypoxic rats decreased Tb (36.15 +/- 0.97 vs. 38.0 +/- 0.36, P < 0.05) whereas Tb was maintained in the exercising hypoxic rats during the initial 6 h of exercise (37.61 +/- 0.55 vs. 37.72 +/- 1.25, not significant). After exercise, Tb in hypoxic rats reached a nadir similar to that in sedentary hypoxic rats (35.05 +/- 1.69 vs. 35.03 +/- 1.32, respectively). Tb reached its nadir significantly later in exercising hypoxic vs. sedentary hypoxic rats (10.51 +/- 1.61 vs. 5.36 +/- 1.83 h, respectively; P = 0.002). Significantly greater histopathological damage and water contents were observed in brain and lungs in the exercising hypoxic vs. sedentary hypoxic and normoxic rats. Thus exercise early in hypoxia delays but does not prevent the HTR. Counteracting the HTR early in hypoxia by exercise exacerbates brain and lung damage and edema in the absence of ischemia.     

Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats

The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (T(b)) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (T(br)), which are exposed after lesions. Ultradian rhythms of T(br) (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min after T(br) peaks, after which temperature continued a slow decline (0.02 +/- 0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of T(br) preceded that of SWA by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30 degrees C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased T(br), blunted the amplitude of ultradian T(br) rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average T(b) within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or T(b) during deviations in ambient temperature.     

The effect of 2G on mouse circadian rhythms

This study examined the effect of chronic 2G exposure on the regulation of body temperature (T(b)), activity (ACT), and circadian rhythms of mice. Five mice were implanted with biotelemetry units to record T(b) and ACT. The mice exhibited a stable daily mean of T(b) (37.1 +/- 2.1 degrees C) and ACT and robust circadian rhythms during the control 1G period. Mice exhibited a significant decline in T(b) (30.1 +/- 1.5 degrees C; t(4)=8.32, p<.01) and cessation of ACT within two hours following 2G onset. After 6 hours of continuous 2G exposure there was a recovery in T(b) (34.4 +/- 1.6 degrees C) that remained significantly below that of baseline (t(4)=3.66, p<.05). A similar pattern of recovery was seen following 12 hours of continuous 2G for ACT. A slower pattern of adaptation toward baseline levels occurred steadily over the next 6-13 days. Exposure to 2G also caused an immediate 4 day loss in circadian rhythm amplitude in both T(b) and ACT. Recovery to new steady state levels was achieved by 8 days and 13 days, respectively. These results demonstrate that under chronic 2G, the recovery time for the homeostatic steady-state values and circadian rhythms are shorter for the mouse than for the rat. These differences may be related to the scaling effects of 2G resulting from the mass difference between mice and rats.     

The circadian body temperature rhythm in the elderly: effect of single daily melatonin dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age-dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age-dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra- and inter-individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38+/-0.19 degrees C vs. 36.17+/-0.21 degrees C) and circadian amplitude (0.33+/-0.01 degrees C vs. 0.26+/-0.01 degrees C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19+/-1.66 vs. 16.93+/-3.08 h). However, the inter-individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter-daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1 degrees C and the amplitude increased to 0.34+/-0.01 degrees C, a similar value to that found in young adults. This was probably due to the increase of the inter-daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter-individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age-dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep-improving effects.     

Behavioral thermoregulation in obese and lean Zucker rats in a thermal gradient

Genetically obese Zucker (Z) rats have been reported to display a body core temperature (Tb) that is consistently below that of their lean littermates. We asked the question whether the lower Tb was a result of deficits in thermoregulation or a downward resetting of the set point for Tb. For a period of 45 consecutive hours, lean and obese Z rats were free to move within a thermal gradient with an ambient temperature (T(a)) range of 15-35 degrees C, while subjected to a 12:12-h light-dark cycle. Tb was measured using a miniature radio transmitter implanted within the peritoneal cavity. Oxygen consumption (VO2) was measured using an open flow technique. Movements and most frequently occupied position in the gradient (preferred T(a)) were recorded using a series of infrared phototransmitters. Obese Z rats were compared with lean Z rats matched for either age (A) or body mass (M). Our results show that obese Z rats have a lower Tb [37.1 +/- 0.1 degrees C (SD) vs. 37.3 +/- 0.1 degrees C, P < 0.001] and a lower VO2 (25.3 +/- 1.9 ml x kg(-1) x h(-1)) than lean controls [33.1 +/- 3.7 (A) and 33.9 +/- 3.9 (M) ml x kg(-1) x h(-1), P < 0.001]. Also, the obese Z rats consistently chose to occupy a cooler T(a) [20.9 +/- 0.6 degrees C vs. 22.7 +/- 0.6 degrees C (A) and 22.5 +/- 0.7 degrees C (M), P < 0.001] in the thermal gradient. This suggests a lower set point for Tb in the obese Z rat, as they refused the option to select a warmer T(a) that might allow them to counteract any thermoregulatory deficiency that could lead to a low Tb. Although all rats followed a definite circadian rhythm for both Tb and VO2, there was no discernible circadian pattern for preferred T(a) in either obese or lean rats. Obese Z rats tended to show a far less definite light-dark activity cycle compared with lean rats.     

Hypoxic depression of circadian rhythms in adult rats.

Because the circadian rhythms of oxygen consumption (VO(2)) and body temperature (T(b)) could be contributed to by differences in thermogenesis and because hypoxia depresses thermogenesis in its various forms, we tested the hypothesis that hypoxia blunts the normal daily oscillations in VO(2) and T(b). Adult rats were instrumented for measurements of T(b) and activity by telemetry; VO(2) was measured by an open-flow method. Animals were exposed to normoxia (21% O(2)), hypoxia (10.5% O(2)), and normoxia again, each 1 wk in duration, in either a 12:12-h light-dark cycle ("synchronized") or constant light ("free running"). In this latter case, the period of the cycle was approximately 25 h. In synchronized conditions, hypoxia almost eliminated the T(b) circadian oscillation, because of the blunting of the T(b) rise during the dark phase. On return to normoxia, T(b) rapidly increased toward the maximum normoxic values, and the normal cycle was then reestablished. In hypoxia, the amplitude of the activity and VO(2) oscillations averaged, respectively, 37 and 56% of normoxia. In free-running conditions, on return to normoxia the rhythm was reestablished at the expected phase of the cycle. Hence, the action of hypoxia was not on the clock itself but probably at the hypothalamic centers of thermoregulation. Hyperoxia (40% O(2)) or hypercapnia (3% CO(2)) had no significant effects on circadian oscillations, indicating that the effects of hypoxia did not reflect an undifferentiated response to changes in environmental gases. Modifications of the metabolism and T(b) rhythms during hypoxia could be at the origin of sleep disturbances in cardiorespiratory patients and at high altitude.     

Hypothermia versus torpor in response to cold stress in the native Australian mouse Pseudomys hermannsburgensis and the introduced house mouse Mus musculus

This study compared torpor as a response to food deprivation and low ambient temperature for the introduced house mouse (Mus musculus) and the Australian endemic sandy inland mouse (Pseudomys hermannsburgensis). The house mouse (mass 13.0+/-0.48 g) had a normothermic body temperature of 34.0+/-0.20 degrees C at ambient temperatures from 5 degrees C to 30 degrees C and a basal metabolic rate at 30 degrees C of 2.29+/-0.07 mL O2 g(-1) h(-1). It used torpor with spontaneous arousal at low ambient temperatures; body temperature during torpor was 20.5+/-3.30 degrees C at 15 degrees C. The sandy inland mouse (mass 11.7+/-0.16 g) had a normothermic T(b) of 33.0+/-0.38 degrees C between T(a) of 5 degrees C to 30 degrees C, and a BMR of 1.45+/-0.26 mL O2 g(-1) h(-1) at 30 degrees C. They became hypothermic at low T(a) (T(b) about 17.3 degrees C at T(a)=15 degrees C), but did not spontaneously arouse. They did, however, survive and become normothermic if returned to room temperature (23 degrees C). We conclude that this is hypothermia, not torpor. Consequently, house mice (Subfamily Murinae) appear to use torpor as an energy conservation strategy whereas sandy inland mice (Subfamily Conilurinae) do not, but can survive hypothermia. This may reflect a general phylogenetic pattern of metabolic reduction in rodents. On the other hand, this may be related to differences in the social structure of house mice (solitary) and sandy inland mice (communal).     

Temporal organisation of hibernation in wild-type and tau mutant Syrian hamsters

The temporal pattern of hibernation was studied in three genotypes of Syrian hamsters with different circadian periodicity to assess a potential circadian control of alternating torpor and euthermy. We recorded the pattern of hibernation by measuring activity in continuous dim light and constant environmental temperature (6 +/- 1 degrees C). In spite of differences in the endogenous circadian period of three genotypes (tau +/+: approximately equals 24 h, tau +/-: approximately equals 22 h, and tau -/-: approximately equals 20 h) torpor bout duration was statistically indistinguishable (tau +/+: 86.9+/-5.3 h; tau +/-: 94.2+/-3.3 h; tau -/-: 88.8+/-6.2 h). The time between two consecutive arousals from torpor showed unimodal distributions not significantly different between genotypes. The first entry into torpor occurred within the active phase of the circadian cycle in all genotypes whereas the first arousal from torpor appeared to be timed randomly with respect to the prior circadian cycle. The amplitude of the activity rhythm was lower after hibernation compared with the amplitude before hibernation. The results suggest that in the Syrian hamster the circadian system does not control periodicity of torpor and arousal onsets in prolonged hibernation at 6 degrees C.     

Physiological significance of cyclic changes in room temperature around dusk and dawn for circadian rhythms of core and skin temperature, urinary 6-hydroxymelatonin sulfate, and waking sensation just after rising

The present study investigated whether room temperature (T(a)) cycles around dusk and dawn could influence the circadian rhythm of rectal temperature (T(core)), urinary 6-hydroxymelatonin sulfate during nocturnal sleep, and subjective assessments of sleep in humans. Six female and two male students served as participants. Two different T(a) conditions, cyclic and constant, were established. Two kinds of room temperature were provided to subjects: cyclic T(a) (gradual decrease from 27 degrees C to 24 degrees C between 1800 and 2200 h and gradual increase from 24 degrees C to 27 degrees C between 0300 and 0700 h) and constant T(a) (27 degrees C over 24 h). At cyclic T(a), the circadian nadir of T(core) rhythm was significantly advanced, while T(core) was significantly lower from 2300 to 0200 h and significantly higher from 0600 to 1000 h. The nocturnal concentration of 6-hydroxymelatonin sulfate in the urine during sleep was significantly higher during cyclic T(a). Waking sensation just after rising was significantly better with cyclic T(a). (Skin temperatures in the extremities-T(a)) were significantly higher with cyclic T(a) especially during the evening and night. Our results suggest that gradual change of room temperature in the evening and early morning is important in terms of sleep promotion and fresh awakening. It seems probable that mankind has been evolved to have deeper sleep under the influence of cyclic T(a) around dusk and dawn.     

AMP does not induce torpor

Torpor, a state characterized by a well-orchestrated reduction of metabolic rate and body temperature (T(b)), is employed for energetic savings by organisms throughout the animal kingdom. The nucleotide AMP has recently been purported to be a primary regulator of torpor in mice, as circulating AMP is elevated in the fasted state, and administration of AMP causes severe hypothermia. However, we have found that the characteristics and parameters of the hypothermia induced by AMP were dissimilar to those of fasting-induced torpor bouts in mice. Although administration of AMP induced hypothermia (minimum T(b) = 25.2 +/- 0.6 degrees C) similar to the depth of fasting-induced torpor (24.9 +/- 1.5 degrees C), ADP and ATP were equally effective in lowering T(b) (minimum T(b): 24.8 +/- 0.9 degrees C and 24.0 +/- 0.5 degrees C, respectively). The maximum rate of T(b) fall into hypothermia was significantly faster with injection of adenine nucleotides (AMP: -0.24 +/- 0.03; ADP: -0.24 +/- 0.02; ATP: -0.25 +/- 0.03 degrees C/min) than during fasting-induced torpor (-0.13 +/- 0.02 degrees C/min). Heart rate decreased from 755 +/- 15 to 268 +/- 17 beats per minute (bpm) within 1 min of AMP administration, unlike that observed during torpor (from 646 +/- 21 to 294 +/- 19 bpm over 35 min). Finally, the hypothermic effect of AMP was blunted with preadministration of an adenosine receptor blocker, suggesting that AMP action on T(b) is mediated via the adenosine receptor. These data suggest that injection of adenine nucleotides into mice induces a reversible hypothermic state that is unrelated to fasting-induced torpor.     

Regulation of the 24h body temperature rhythm of women in luteal phase: role of gonadal steroids and prostaglandins

An investigation into whether the rise in the 24h body temperature rhythm observed in the luteal menstrual phase is antagonized by the administration of prostaglandin synthesis inhibitors has been made. Intravaginal body temperature was monitored continuously for 24h, once in the follicular and twice in the luteal phase. In the luteal phase, women were studied both without and with the simultaneous administration of a prostaglandin synthesis inhibitor (lysine acetylsalicylate; 1.8 g every 6 h orally). The progesterone/estradiol ratio (measured at 17:00h each day) was related to mesor (r = 0.825; P < 0.001), acrophase (r = 0.682; P < 0.02), and amplitude (r = -0.731; P < 0.001) of the 24h body temperature rhythm. Luteal phase elevation of the progesterone/estradiol ratio was associated with a 0.32 +/- 0.07 degrees C increase in mesor (P < 0.01), a 0.11 +/- 0.02 degrees C decrease in amplitude (P < 0.001), and a 34.8 +/- 11.6 min delay in acrophase (P < 0.03) of the 24h body temperature rhythm. Prostaglandin synthesis inhibitors did not counteract these modifications. The present data shows that the modifications of the circadian parameters of the 24h body temperature rhythm observed during the luteal phase of the menstrual cycle are strictly related to modifications of the progesterone/estradiol ratio, and presumably independent of prostaglandin synthesis.     

Low doses of melatonin and diurnal effects on thermoregulation and tolerance to uncompensable heat stress.

This study examined whether the reported hypothermic effect of melatonin ingestion increased tolerance to exercise at 40 degrees C, for trials conducted either in the morning or afternoon, while subjects were wearing protective clothing. Nine men performed four randomly ordered trials; two each in the morning (0930) and afternoon (1330) after the double-blind ingestion of either two placebo capsules or two 1-mg capsules of melatonin. Despite significant elevations in plasma melatonin to over 1,000 ng/ml 1 h after the ingestion of the first 1-mg dose, rectal temperature (T(re)) was unchanged before or during the heat-stress exposure. Also, all other indexes of temperature regulation and the heart rate response during the uncompensable heat stress were unaffected by the ingestion of melatonin. Initial T(re) was increased during the afternoon (37.1 +/- 0.2 degrees C), compared with the morning (36.8 +/- 0.2 degrees C) exposures, and these differences remained throughout the uncompensable heat stress, such that final T(re) was also increased for the afternoon (39.2 +/- 0.2 degrees C) vs. the morning (39.0 +/- 0.3 degrees C) trials. Tolerance times and heat storage were not different among the exposures at approximately 110 min and 16 kJ/kg, respectively. It was concluded that this low dose of melatonin had no impact on tolerance to uncompensable heat stress and that trials conducted in the early afternoon were associated with an increased T(re) tolerated at exhaustion that offset the circadian influence on resting T(re) and thus maintained tolerance times similar to those of trials conducted in the morning.     

Seasonal rhythms of body temperature in the free-ranging raccoon dog (Nyctereutes procyonoides) with special emphasis on winter sleep

The raccoon dog (Nyctereutes procyonoides) is the only canid with passive overwintering in areas with cold winters, but the depth and rhythmicity of wintertime hypothermia in the wild raccoon dog are unknown. To study the seasonal rhythms of body temperature (T(b)), seven free-ranging animals were captured and implanted with intra-abdominal T(b) loggers and radio-tracked during years 2004-2006. The average size of the home ranges was 306+/-26 ha, and the average 24 h T(b) was 38.0+/-<0.01 degrees C during the snow-free period (May-November). The highest and lowest T(b) were usually recorded around midnight (21:00-02:00 h) and between 05:00-11:00 h, respectively, and the range of the 24 h oscillations was 1.2+/-0.01 degrees C. The animals lost approximately 43+/-6% of body mass in winter (December-April), when the average size of the home ranges was 372+/-108 ha. During the 2-9-wk periods of passivity in January-March, the average 24 h T(b) decreased by 1.4-2.1 degrees C compared to the snow-free period. The raccoon dogs were hypothermic for 5 h in the morning (06:00-11:00 h), whereas the highest T(b) values were recorded between 16:00-23:00 h. The range of the 24 h oscillations increased by approximately 0.6 degrees C, and the rhythmicity was more pronounced than in the snow-free period. The ambient temperature and depth of snow cover were important determinants of the seasonal T(b) rhythms. The overwintering strategy of the raccoon dog resembled the patterns of winter sleep in bears and badgers, but the wintertime passivity of the species was more intermittent and the decrease in the T(b) less pronounced.     

Unequal coupling between locomotor pacemakers of the German cockroach,Blattella germanica (L.)

Male adult German cockroaches, Blattella germanica (L.), expressed robust locomotor circadian rhythmicity under 28 degrees C and constant darkness (DD) conditions. By surgically severing the connections between the optic lobes and midbrain and their subsequent regeneration, we demonstrated that the locomotor circadian pacemaker was located in the optic lobes and that it controlled the locomotor circadian rhythm through neural pathways. From the results that unilaterally optic tract severed males still showed locomotor circadian rhythmicity (93.1%, n=29) without significantly changing the circadian period (tau) or level of motor activity, we concluded that the right and left optic lobes each contain a circadian pacemaker competent to drive the locomotor circadian rhythm. These two pacemakers were strongly coupled since only one rhythm was expressed when the pacemakers were independently exposed to opposite lighting conditions (DD or LL) at the same time. However, an unequal contribution of each pacemaker in determining the overt circadian period was found under constant dim light (10 lux) conditions, revealing a major-minor coupling relationship between these two pacemakers, so that the unilaterally blinded male expressed either a LL-rhythm with a circadian period of 24.27+/-0.21 h (41.7%, n=24) or a DD-rhythm with a circadian period of 23.43+/-0.19 h (58.3%, n=24). However, higher intensity of photic information (200-300 lux) could overpower this relationship and cause the minor pacemaker to lead the rhythm.     

Effects of temperature and temperature-steps on circadian locomotor rhythmicity in the blow fly Calliphora vicina

The free-running period (in darkness) of the locomotor activity rhythm in adult blow flies (Calliphora vicina) was temperature-compensated between 15 and 25 degrees C, showing Q(10) values between 0.98 and 1.04. Single steps-up (20 to 25 degrees C) or steps-down (20 to 15 degrees C) in temperature caused stable phase shifts of the activity rhythm, giving rise to temperature-step phase response curves (PRCs) with both advances and delays. Phase advances, however, were dominant for steps-up, and phase delays for steps-down; the two PRCs were almost "mirror images" of each other. Following protocols introduced by Zimmerman et al. [(1968) Temperature compensation of the circadian oscillation in Drosophila pseudoobscura and its entrainment by temperature cycles, Journal of Insect Physiology, 14, 669-684] for the rhythm of pupal eclosion in Drosophila pseudoobscura, the steps-up and steps-down PRCs for C. vicina were used to compute a theoretical PRC for a 6 h low temperature pulse, and from this a theoretical steady-state phase relationship of the locomotor activity rhythm to a train of such pulses making up a temperature cycle (18 h at 20 degrees and 6 h at 15 degrees C).     

Chronopharmacology of pancuronium in rats anesthetized by CT 1341 (Alfatésine)]

A circadian variation in the curarizing ability of pancuronium bromide (Pavulon) has been documented in an homogenous group of 100 Wistar AF-SPF adult male rats anaesthetized by the steroid anaesthetic althesin (Alfatésine, CT 1341). Animals were maintained at 24 +/- 2 degrees C and synchronized with natural light 06.00 to 18.00 and darkness (october 1977). We observed significant circadian rhythms for both of these agents: first the induction of anaesthesia by althesin was markedly pronounced at 15.30 and varied with season. Secondly the maximum effect of pancuronium was recorded at 08.00. When rats were anaesthetized by sodium pentobarbital under similar experimental conditions but during a different season (january to may) we observed a similar circadian rhythm for pancuronium. These data indicate that: a) the type of anaesthesia used in the protocol may not be of importance in demonstration of a curarizing rhythm in the rat but, b) the possibility of a seasonal component being present and effecting this rhythm needs to be investigated.     

Modification of the hypothermic circadian cycles induced by DSIP and melatonin in pinealectomized and hypophysectomized rats

Both melatonin and DSIP (a nine amino acid peptide) effects have been previously shown to be (a) circadian rhythm related and (b) involved in inducing hypothermic effects in rats. In this study we report the hypothermia effects by each of these drugs alone and in combination when studied in normal (unoperated), pinealectomized, and hypophysectomized rats at various time points of the corresponding circadian cycle. A clear differential effect of drugs × time × preparation was found. While both DSIP and melatonin hypothermic effects were both circadian cycle dependent in intact rats the rhythmicity of melatonin hypothermic effect in pinealectomized rats, and DSIP hypothermic effect in hypophysectomized rats was missing. Although several hypotheses have been offered to account for the physiological mechanism(s) that govern the effects of the drugs, it is not yet possible to reliably relate the findings to existing neurochemical theory.     

Circadian temperature rhythms in rabbit pups and in their does.

Circadian rhythms of mammals are generated endogenously, the master oscillator system residing in the suprachiasmatic nuclei (SCN). Previous experiments have indicated that the rabbit has a feeding entrainable circadian oscillator (FEO) which is supposed to be of greatest importance during the early infancy of the rabbit. Here we report the course of telemetrically monitored core body temperature of rabbit pups and of their does. Temperature increased from 37.6+/-0.3 degrees C on day 2 to 39.5+/-0.1 degrees C on day 28 of life. The pups showed a 24 h temperature rhythm even during their first days of life. Temperature increased 2 1/2-3 h prior to nursing for 0.4-0.8 degrees C and rose for an additional 0.4-0.6 degrees C immediately after milk ingestion. The anticipatory, but not the postprandial component persisted when nursing was skipped twice. The persistence of a rhythm in the absence of any entraining agent is crucial for its endogenous generation. In the doe, the core body temperature gradually decreased during the last 2/3 of pregnancy. During parturition it steeply rose for 1.5-1.7 degrees C and attained a plateau of 39.7+/-0.2 degrees C during lactation. The circadian rhythm persisted during the whole course of pregnancy and lactation. Thus, in the rabbit an endogenous, feeding entrainable circadian oscillator appears to operate from the first days of life. It is of functional significance in that it alerts the pup in time so that it is able to utilize the singular short presence of the doe for maximal milk intake.