Intraperitoneal Temperature Research Articles

Continuous exposure to dim illumination uncouples temporal patterns of sleep, body temperature, locomotion and drinking behavior in the rat

Dissociable circadian rhythms of sleep and body temperature in primates are thought to be regulated by independent oscillators whereas the uncoupling of circadian rhythms has not been well described in other mammals. Therefore, we made simultaneous recordings of non-rapid-eye-movement-sleep (NREMS), rapid-eye-movement-sleep (REMS), brain temperature, intraperitoneal temperature, locomotion and drinking activity under light-dark (LD) and continuous dim illumination (dim LL) and analyzed their interrelations. The rhythmic patterns of body temperature, locomotion and drinking were modified on the 12th circadian day of dim LL, while the mean body temperature as well as mean occurrence of drinking and locomotor activities did not change significantly. In contrast, dim LL exposure significantly increased the total time spent in NREMS during the resting phase of dim LL and increased REMS episodes during the active phase of dim LL. The diverse effects of dim LL exposure on the recorded phenomena suggest that temporal patterns of sleep were the most sensitive to perturbations of lighting and that differential oscillatory mechanisms may regulate sleep and other circadian rhythms in the rat.

Amplitude of the daily rhythm of body temperature in eleven mammalian species

The amplitude of the daily rhythm of body temperature was investigated in 11 species of small mammals. Recording equipment, housing and environmental conditions were identical for all species. Intraperitoneal temperature was measured by telemetry at 6 min intervals for 10 or more days. The results indicate that the amplitude of the body temperature rhythm is a species-specific trait in small mammals. Interspecies differences in amplitude are not a function of surface area (as determined by body size) but seem to relate to diurnality (nocturnal species displaying smaller amplitude than diurnal ones) and habitat (species from temperate habitats displaying smaller amplitude than species from desert and tropical habitats).

Behavioral approach to the study of the upper limit of temperature tolerance in rats

Caputa, M., K. Dokładny and B. Kurowicka. Behavioral approach to the study of the upper limit of temperature tolerance in rats. PHYSIOL BEHAV 65(1) 183–189, 1998.—A simple test of critical thermal maximum (CTM) to assess a break-down of heat-escape behavior in rats is described. Experiments were performed on 18 unrestrained adult Wistar rats of both sexes. Hypothalamic and intraperitoneal (i.p.) temperatures as well as motor activity were simultaneously and continuously recorded in the rats exposed to heat. When animals were growing restless, as evidenced by an increase in their motor activity, which was usually recorded at hypothalamic temperatures well above 41°C, we started testing CTM. To assess heat-escape behavior we used a precooled cooling bar (a part of a camp-cooler) which was placed at intervals in a climatic chamber. The hyperthermic rats, given the bar for 30 s, mounted it vigorously until they failed at particular levels of brain and body temperatures which were recognized as respective CTM values. Rapid external cooling of rats prevented lethal effects of the heat exposure. We were able to show effects of timing of heat exposure on heat tolerance. We also managed to detect small but significant differences in heat tolerance of warm-reared (an increase), cold-reared (a decrease), and bacterial–endotoxin-treated (an increase) rats. The heat-escape behavior was less heat-resistant than selective brain cooling response which was still present at CTM point. In conclusion, our CTM test is a safe and reliable way to study heat tolerance in rats.

Simultaneous Recording of Circadian Rhythms of Brain and Intraperitoneal Temperatures and Locomotor and Drinking Activities in the Rat

In order to investigate the circadian oscillatory system, the present study performed simultaneous and continuous recordings of brain and intraperitoneal temperatures, drinking and locomotion in rats under light-dark (LD) cycles and continuous dim illumination (dim LL) for a total period of 16 days. Compared to circadian amplitudes under LD, those under dim LL were significantly reduced by 34% for drinking and 50% for locomotion, but were not for brain and intraperitoneal temperatures. On the other hand, means of steady circadian periods during last 10 days under dim LL were all within a close range between 24.2 and 24.3 h in these rhythms. Besides the steady periods, one rat exhibited weak circadian period of 23.7 and 24.6 h, but these multiple frequencies were also equally observed in the four rhythms. The similarity in the periodicities suggests that these temperature and activity rhythms might be driven by a common oscillatory system. Therefore differential reductions in the amplitudes of drinking and loc omotor rhythms might be caused by a masking effect of dim LL on their rhythm output-pathways. Hence rats may temporally coordinate various physiological and behavioral functions by such clock system under time cue free environment.

Operant control of ambient temperature during sleep deprivation.

Rats subjected to total sleep deprivation (TSD) by the disk-over-water method were provided with a continuously available operant by which they could increase ambient temperature (T(amb)). TSD rats progressively increased operant responses for heat to 700% of baseline levels. During the last quarter of sleep deprivation, they maintained mean T(amb) at 9 degrees C above baseline and held T(amb) over 40 degrees C for 35% of the day. In contrast, yoked control rats (TSC) did not change mean T(amb). Although both TSD and TSC rats showed a progressive decline in intraperitoneal temperature (T(ip)), TSD rats maintained an elevated T(amb) even during periods when T(ip) and brain temperatures (T(br)) were above baseline levels. Thus these results confirm and extend earlier findings that rats subjected to TSD show an increase in temperature set point (T(set)). The earlier studies, which utilized short daily trials in a thermal gradient, demonstrated an increase in T(set) early in the deprivation period. The present study, which obtained more extensive data on thermal preference at a range of body temperatures demonstrated an increasing T(amb) for almost all T(ip) and T(br) values, suggesting a progressive increase in T(set) over the course of sleep deprivation. Surprisingly, survival time was shorter than in previous TSD studies. Reduced survival could not be attributed to differences in T(br), T(ip), energy expenditure, or sleep loss from previous studies.

Intraperitoneal Temperature of Piglets in the First Three Postnatal Weeks as Measured by Radiotelemetry

Baranyiova E .. A. Holub, R. L. Hullinger: Intraperitoneal TemperatureoJPiglets in the First Three Postnatal Weeks as Measured by Radiotelemetry. Acta vet. Bmo, 1997,66:3-8. Intraperitoneal temperature (IT) was detennined in early-weaned piglets of both sexes to day 21, using radiotelemetry. Ten piglets (five weaned on the second, five on the third day after birth), were used in the study. They were reared individually in cages, offered a liquid diet for suckling at 2-h intervals 9 times a day. They were placed in a temperature-controlled room with L:D regime of 12:12 h. Audio signals from intraperitoneally implanted transmitters (Minimitter Co., Sunriver, OR, USA) were converted to body temperature using calibration data. A total of 1,963 daily measurements taken between 06.00 and 22.00 h show that in the first two postnatal weeks the mean daily IT rose significantly (P < 0.05) with advancing age from 39.8 ± 0.1 °C to 40.5 °C. At the beginning of the second week, there was a transient IT decrease, followed by another increase; IT did not change thereafter. There were also diurnal changes in IT observed in the light phase, especially during the morning hours. IT was also affected by gender. In males the mean daily IT was higher, though not significantly. during the entire experimental period. During dietary intake there was a small temporary increase in IT. An IT elevation occurred in several piglets suffering from transient diarrhoea. Radiotelemetric procedures with unrestrained animals exclude measurement errors resulting from direct contact with the measuring techniques/devices and the excitement due to contact with experimenters. Radiotelemetry opens new technical possibilities of a reliable, undisturbed recording of body temperature in piglets. Early weaning, core body temperature. individual rearing. temperature regulation. radiotelemetry

CONTINUOUS HYPERTHERMIC PERITONEAL PERFUSION THERAPY COMBINED WITH PARAAORTIC LYMPH NODE DISSECTION FOR SEROSAL EXPOSED GASTRIC CANCER

The aim of this study is to evaluate the usefulness of intraoperative continuous hyperthermic peritoneal perfusion therapy (CHPP) combined with paraaortic lymph node dissection for the patients with serosal exposed gastric cancer. The survival and recurrent rates between CHPP combined (CHPP(+)) group (n=29) and CHPP not combined (CHPP(-)) group (n=35) were discussed. In 7 peritoneal disseminated cases the apoptosis index before and after CHPP were examined at several lesions of peritoneal dissemination. The 3-year survival rates were 42.6% in CHPP(+) group and 46.4% in CHPP(-) group and the rates in n4(-) cases were 72.5% and 48.1% respectively. The rates of peritoneal recurrence were 31.0% in CHPP(+) group and 34.3% in CHPP(-) group. Especially in the n4(-) cases, the rates were 16.7% in CHPP(+) and 30.8% in CHPP(-). And no peritoneal recurrence was observed in n4(-) cases with the mean intraperitoneal temperature was more than 42°C. The apoptosis index was 3.5±2.3% before CHPP or 51.5±7.5% after CHPP. In conclusion, CHPP is effective as a local therapy and paraaortic node dissection combined with CHPP is useful for the patients with no paraaortic lymph node metastasis and those whose mean intraperitoneal temperature had been maintained at more than 42°C.

Relationship between cold-induced thermoregulation and spontaneous rapid body weight loss of aging F344 rats.

We previously showed that, although cold-induced thermoregulation is attenuated in 26-mo-old male Fischer 344 (F344) rats, not all rats this age exhibit the same degree of cold-exposed hypothermia or diminished brown adipose tissue nonshivering thermogenic capacity. Examination of this heterogeneity suggested the hypothesis that it was associated with a difference in the physiological state between aged rats that were maintaining stable body weight versus those showing the rapid weight loss often occurring near the end of the rat's natural life span. To test this, we acutely exposed male F344 rats to cold (4 h at 6 degrees C) beginning at 24 mo of age. This exposure was weekly for the first 2 wk and then on alternate weeks as long as the rat's body weight was stable. If body weight progressively declined for 3-5 consecutive days, the rat's response to the acute cold exposure was again measured, as was that of two additional rats not displaying this rapid loss in body weight. If body temperature decreased during the cold exposure to intraperitoneal temperatures < or = 32.5 degrees C, the rat was killed with pentobarbital sodium and interscapular brown adipose tissue was removed. One of the age-matched controls was also killed at this time. The age at which body weight showed a spontaneous rapid decline ranged from 24.5 to 29 mos. All eight rats displaying spontaneous rapid weight loss had significant hypothermia during the acute cold exposure, whereas none of the eight weight-stable rats did. The development of hypothermia in the spontaneous rapid weight loss group was not, in general, observed before their weight loss. The weight loss and hypothermia were associated with lower levels of brown fat uncoupling protein and significant changes in body fat and protein. These data suggest that the development of senescence-related hypothermia occurs rapidly and is not a simple function of chronological age or the median life span of the animals. Furthermore, these data imply that the rate of aging in terms of maintenance of thermoregulatory homeostasis has both a gradual and rapid component, the latter being associated with a different physiological state than the former.

Abdomino-pelvic hypertherma and intraperitoneal carboplatin in epithelial ovarian cancer: Feasibility, tolerance and pharmacology

Purpose: To investigate the feasibility, toxicity, and pharmacokinetics of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic hyperthermia (HT) in advanced ovarian cancer patients. Methods and Materials: Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initial course of i.p. CB for baseline pharmacokinetics followed by three cycles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature >42° but <50°C while maintaining normal tissue temperatures <43°C and systemic body temperatures <38°C. No analgesic premedication was used. Thermometry was recorded by multisensor fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. Results: Thirteen patients received a total of 31 sessions. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal temperatures >40°C, for more than 40 min in 7 31 sessions. The average values of thermal variables were T 90 = 40°C, T AVE = 41°C, T MIN = 38.2°C, and T MAX = 42.9°C. The mean maximum systemic temperature was 38°C. Acute thermal toxicities requiring early interruption of hyperthermia were systemic temperature exceeding 38°C (11 of 31), abdominal pain or generalized distress (20 of 31), and vomiting (2 of 31). Hematologial toxicities were not increased by hyperthermia. Pharmacokinetics were consistent with enhanced clearance of CB by HT. Lower radio frequencies (<75 MHz) achieved better heat deposition in the peritoneal cavity than higher frequencies (>75 MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with no evidence of disease at 40 and 43 months from treatment. Conclusions: Intraperitoneal temperatures in the range of 40°C maintained for approximately 40 min can be achieved within the described setting. The probability of successful induction of therapeutic intraperitoneal temperatures appears to be higher when frequencies below 75 MHz are used. Patients who are potentially platinum sensitive and have minimal residual disease could potentially benefit from the combined treatment under the conditions studied. However, this temperature-time range appears inadequate against platinum resistant disease, and/or bulky residual pelvic disease. Alternative approaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed.

Stress induced disorganization of circadian and ultradian rhythms: Comparisons of effects of surgery and social stress

Persistent autonomic disturbances following stressful events suggest that the rhythmical nature of homeostatic functioning may be disrupted by these experiences. We assessed the effects of two different stressors on circadian and ultradian rhythms of Long-Evans rats by using nonlinear multi-oscillator cosinor analysis. Heart rate and intraperitoneal temperature were monitored continuously in 5-min intervals in two groups of animals via radio-telemetry for 15 days after surgery ( n = 9) and 15 days following social defeat ( n = 6). Circadian amplitude of heart rate and temperature increased significantly for the first nine days of the recovery from surgery but only circadian temperature amplitude increased following social defeat. Circadian acrophase of temperature but not heart rate changed significantly for a similar period following the surgery but not after the social defeat. A mathematical model incorporating the first five harmonics of the circadian rhythm was found to fit the data significantly better than a circadian model alone with rhythms of 3 and 5 cycles/day in temperature and heart rate entraining significantly to the light-dark schedule. Full recovery of the circadian and ultradian rhythms did not occur until a minimum of nine to twelve days after surgery or social defeat. The results suggest that rhythms with multiple periodicities are involved in homeostatic functioning and that models incorporating these rhythms may aid in understanding an organisms adaptive response to surgical intervention and social defeat, long after the challenges have terminated.

Day-night variations of behavioral and autonomic thermoregulatory responses to lipopolysaccharide in rats.

This study investigated the day-night differences in behavioral and autonomic thermoregulatory responses to bacterial lipopolysaccharide (LPS) in rats. Male rats were housed individually in cages with a 12: 12 h light dark cycle at an ambient temperature of 24 degrees C. The rats were placed in a box with a temperature gradient and intraperitoneally injected with LPS (10 micrograms/kg). The preferred ambient temperature (Tpr) was estimated by the location of the rats in the box, and intraperitoneal temperature (Tb) was measured by a biotelemetry system. Measurements were taken during the light and dark phases of the day. LPS produced fever in both phases. The magnitude of rise in Tb did not differ between the two periods. In the dark phase, Tpr significantly increased during the development of fever and decreased during the defervescence, while it did not change throughout the febrile course during the light phase. In a separate experiment, rats were loosely restrained and placed in a direct calorimeter. Their colonic temperature (Tcol), evaporative and nonevaporative heat loss and heat production were measured before and after intraperitoneal injections of LPS (10 micrograms/kg). Measurements were taken during the light and dark phases of the day. LPS induced fever in both phases. The magnitude of change in T col, heat loss, and heat production due to LPS did not differ between the two periods. These results suggest that the fertile response of rats to intraperitoneal LPS is not affected by the time of day. However, it seems that during LPS-induced fever, thermoregulatory behavior is not fully activated during the light phase of the day.

Intraoperative hyperthermic lavage with cisplatin for peritoneal carcinomatosis and sarcomatosis.

Intraoperative hyperthermic lavage with cisplatin was studied in 8 patients with peritoneal carcinomatosis and sarcomatosis. A dose of 50 mg/m2 of cisplatin used for 2 hours with an intraperitoneal temperature of 41 degrees to 43 degrees C was used. Pharmacokinetic studies showed that cisplatin left the abdomen and pelvis by simple diffusion with a half life of 48 minutes in the peritoneal fluid. Eighty-six percent of the drug was absorbed into the plasma within 2 hours but only 6.9% was excreted into the urine. The area under the curve ratio for peritoneal fluid to plasma was 6.9. The quantity of cisplatin in tissue from the abdomen or pelvis was extremely variable. It was 1.85-10.28 micrograms cisplatin/g tumor and < 0.57-7.90 micrograms/g normal tissue. Comparison of pharmacologic parameters of hyperthermic to normothermic cisplatin administration showed no significant differences.

Effect of experimental left varicocele on rat Leydig cell function

In order to study endocrinological disorders in varicocele, serum hormone (LH, FSH and testosterone) levels, intratesticular temperature, and testicular histology were evaluated in the rats with experimental left varicocele. Testosterone production and its responsiveness to human chorionic gonadotropin (hCG) in isolated Leydig cells were also determined in the model. The varicocele was created by partial ligation of the left renal vein. The mean difference between intratesticular and intraperitoneal temperature and the levels of serum hormones were similar in varicocele-induced and sham-operated rats at either 2 or 4 weeks after surgery. Histological examination using the Johnsen score count method showed defective spermatogenesis at 2 and 4 weeks. In Leydig cell incubation, testosterone levels in the media without hCG were similar in the left testes of varicocele-induced rats (LV), the right testes of varicocele-induced rats (RV), and the testes of sham-operated rats (S) at 2 and 4 weeks. Although the presence of various concentrations of hCG made no difference in testosterone production between LV, RV, and S at 2 weeks, there were significantly decreased elevations in the production at 100 mIU/ml and 1,000 mIU/ml of hCG in LV and RV as compared with that of S at 4 weeks. The bindings of [125I] hCG to Leydig cells from LV and RV were significantly lower than S at 4 weeks. Furthermore, testosterone responsiveness to dibutyryl c-AMP in Leydig cells was similar between LV, RV, and S.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma

Purpose : To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. Methods and Materials : Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5°C. Cisplatin dose started at 20 mg/m 2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. Results : Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m 2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7°C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30–35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. Conclusion : Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80–120 mg/m 2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7°C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.

Kidney trace metal response to combined cisplatin (CDDP) and hyperthermia.

The effects of hyperthermia (HY) on cisplatin (CDDP) nephrotoxicity and kidney metal concentrations were evaluated in female F344 rats. Rats were anaesthetized with a xylazine/ketamine mixture, heated on a water-bed for 1 h to an intraperitoneal temperature of 41.1 +/- 0.2 degrees C, and maintained at hyperthermia for an additional 30 min (HY plateau). CDDP (5 mg/kg body weight) was administered at the start of the heating or at the HY plateau. Neither HY alone nor CDDP (5 mg/kg) at normothermia produced a significant effect on weight loss or nephrotoxicity. CDDP administered at the start of heating produced a moderate 1.5-fold increase in serum urea nitrogen (SUN) and serum creatinine concentrations. CDDP administered at the HY plateau produced a significant six-fold increase in SUN and a four-fold increase in creatinine concentration. Weight loss increased two- to three-fold from the combined regimen, but only the rats given CDDP at the HY plateau continued to lose weight through day 7. A loss of kidney copper (50-60%) resulted from the combined regimen, similar to losses observed with higher doses of CDDP at normothermia. HY alone had little effect on concentrations of kidney copper or zinc up to 4 days post-treatment. The results demonstrate that systemic hyperthermia significantly increases CDDP nephrotoxicity in F344 rats and that kidney copper loss from CDDP exposure at hyperthermia is similar to the loss observed from CDDP at normothermia.

Cerebrospinal fluid pressure in conscious rats during prostaglandin E1 fever

Intraperitoneal body temperature was monitored from groups of 10 conscious adult male Wistar rats. The daily body temperature rhythm was determined, and an intraperitoneal body temperature dose response relationship was established for prostaglandin E1 (PGE1) delivered into a lateral cerebral ventricle (LCV). Cerebrospinal fluid pressure was measured by direct cannulation of a LCV. Heart rate, arterial and central venous blood pressure, and blood gases were also measured in groups of 10 animals. It was found that there was a daily rhythm in intraperitoneal body temperature that was higher at night than during the day but stable between 0800 and 1600 h. A significant temperature dose (20-2,000 ng)-response relationship was established for administration of PGE1 into the LCV. Cerebrospinal fluid pressure when measured from the LCV increased significantly during the "chill" phase of the PGE1-induced fever. Carotid arterial blood pressure also significantly increased at this time as did central venous pressure, particularly so with vigorous shivering. There was a significant fall in arterial CO2 partial pressure, a slight rise in pH, and no change in arterial O2 partial pressure. These data support the hypothesis that a significant increase in cerebrospinal fluid pressure occurs during the chill phase of a PGE1-induced fever in the conscious rat.

Rhythms in behaviors, body temperature and plasma corticosterone in SCN lesioned rats given methamphetamine

In aperiodic rats with lesions in the suprachiasmatic nuclei (SCN), rhythms with a circadian period in spontaneous locomotion, wheel-running, feeding, drinking, body temperature and plasma corticosterone were restored by chronic administration of methamphetamine. These rhythms were not entrained by a light-dark cycle. Wheel-running, feeding and drinking rhythms in individual rats were in phase in terms of ultradian bout as well as circadian fluctuation. Rhythms of the intraperitoneal temperature appeared accompanying the spontaneous locomotor rhythm. The phase relation between the two rhythms was similar to that of SCN dependent rhythms. Plasma corticosterone also fluctuated in a circadian fashion. The corticosterone peak preceded the activity onset of locomotor rhythm by a few hours, which was similar to the phase relation observed in the SCN intact animals. It is concluded that the oscillatory mechanism underlying the spontaneous locomotor rhythm in SCN lesioned and methamphetamine treated rats drives also other physiological rhythms. The phase-relations among them were similar to those of rhythms driven by the circadian pacemaker in the SCN.

Whole-body hyperthermia decreases lung metastases in lung tumor-bearing mice, possibly via a mechanism involving natural killer cells

The effects of whole-body hyperthermia (WBH) on the course of the Lewis lung carcinoma (LLC) and B16 melanoma (B16) were examined. WBH was generated by microwave (2450 MHz) at an intraperitoneal temperature of 39.5-40.0 degrees C and an intratumoral temperature of 40.0-40.5 degrees C for 30 min once a week, X 3 (LLC) or X 6 (B16). The mice were sacrificed 21 days (LLC) or 42 days (B16) after tumor implantation and lung metastases were scored. Natural killer (NK)-cell activity was determined against the YAC-1 tumor target in WBH-treated tumor-bearing mice as well as in tumor-bearing mice but untreated controls. The number of lung metastases was significantly reduced and NK-cell activity was higher in animals treated with WBH. Thus, this study suggests that WBH interferes with the spread of organ metastases, possibly through a mechanism involving NK cells.

Thermoregulation and Oxygen Consumption during Terrestrial Locomotion by White-Crowned Sparrows Zonotrichia leucophrys gambelii

We trained white-crowned sparrows to locomote (normal mixed gait) on the wiremesh substrate of a circular treadmill while we measured steady-state $\dot{V}O_{2}$, evaporative water loss ($\dot{m}_{v}$), and intraperitoneal temperature ($T_{b}$) at several treadmill speeds (0, 0.30, 0.35, 0.41, 0.46 km h⁻¹) and air temperatures ($T_{a}$, 10, 0, 12, and 25 C) at each speed. In birds at rest, $T_{b}$ increased as $T_{a}$ diminished, but $T_{b}$ was independent of $T_{a}$ when birds were locomoting. At any $T_{a}$, $T_{b}$ increased linearly with treadmill speed (to a maximum of 44.1 C). At $T_{a} = 12 C$ or lower, $\dot{V}O_{2}$ was a linear function of $T_{a}$ at all treadmill speeds but did not conform to this regression at $T_{a} = 25 C$ ($\dot{V}O_{2}$ at 0.35-0.46 km h⁻¹ was lower than expected). We hypothesize that $T_{a}$ is not a reliable index of thermal environment in this zone and should be replaced by the operative temperature, $T_{e}$. At all $T_{a}'s$, $\dot{V}O_{2}$ was a linear function of ...

Alpha-methyl-p-tyrosine shifts circadian temperature rhythms.

alpha-Methyl-p-tyrosine shifts the acrophase (time of highest temperature) of the circadian temperature rhythm of the rat to earlier or later times of day depending on the phase of the circadian cycle at which the drug is administered. When alpha-methyl-p-tyrosine methyl ester HCl is injected intraperitoneally at a dose of 100 mg/kg late in the projected 8-h light phase, the acrophase of the intraperitoneal temperature rhythm is delayed by up to 3 h. However, when the same dose of drug is given 9-10 h into the projected 16-h dark phase of the daily cycle, the acrophase of the temperature rhythm occurs about 2 h earlier than expected. The times of alpha-methyl-p-tyrosine administration leading to maximal phase delays or advances are correlated with the times of minimal and maximal turnover of norepinephrine in the hypothalamus. These results suggest that changing rates of norepinephrine turnover in the hypothalamus may regulate the circadian temperature rhythm in rats. The results also emphasize the fact that the effects of drugs may vary as a function of the time of administration. This fact must be taken into account in pharmacologic testing.