Sleep deprivation elevates plasma corticosterone levels in neonatal rats.

Plasma corticosterone (CORT) levels were measured after short periods of sleep deprivation in rats at postnatal days 12, 16, 20, and 24. There was an age-dependent increase in basal CORT levels and sleep deprivation significantly elevated CORT at all ages compared to non-sleep deprived controls. The levels of CORT after sleep deprivation in P16, P20 and P24 animals were similar, resulting in an age-dependent decrease of the magnitude of the response. Sleep deprived P12 animals had lower levels of CORT. However, the observed response to sleep deprivation suggests that sleep loss is a significant stressor at this age. These observations suggest that younger animals are more sensitive to the effects of mild sleep deprivation than older ones.

Siberian hamsters that fail to reentrain to the photocycle have suppressed melatonin levels.

Siberian hamsters readily reentrain to a 3-h phase delay of the photocycle (16 h light/day) but fail to reentrain to a 5-h phase delay. This study tested whether melatonin production was suppressed in animals that failed to reentrain. Melatonin was measured on the day before, day of, or several days after each phase shift. Melatonin levels measured 4 h after dark onset were approximately 83 microg/ml on the day before each phase delay and undetectable (<6 microg/ml) during the light phase on the day of the phase shift. Activity onsets regained their prior phase relationship to the photocycle 4 (3 h) or 5 (5 h) days after the phase shift; on that day, melatonin levels were measured 4 h after dark onset. Melatonin levels were unaffected by the 3-h phase delay (>57.6 microg/ml) but were undetectable after a 5-h phase delay (<8 microg/ml). Thus melatonin remained suppressed only after the phase delay to which hamsters also fail to reentrain. This relationship suggests that the propensity for reentrainment may be influenced by changes in melatonin production following a phase shift of the photocycle.

Circadian rhythms in the suprachiasmatic nucleus are temperature-compensated and phase-shifted by heat pulses in vitro.

Temperature compensation and the effects of heat pulses on rhythm phase were assessed in the suprachiasmatic nucleus (SCN). Circadian neuronal rhythms were recorded from the rat SCN at 37 and 31 degrees C in vitro. Rhythm period was 23.9 +/- 0.1 and 23.7 +/- 0.1 hr at 37 and 31 degrees C, respectively; the Q(10) for tau was 0.99. Heat pulses were administered at various circadian times (CTs) by increasing SCN temperature from 34 to 37 degrees C for 2 hr. Phase delays and advances were observed during early and late subjective night, respectively, and no phase shifts were obtained during midsubjective day. Maximum phase delays of 2.2 +/- 0.3 hr were obtained at CT 14, and maximum phase advances of 3.5 +/- 0.2 hr were obtained at CT 20. Phase delays were not blocked by a combination of NMDA [AP-5 (100 microM)] and non-NMDA [CNQX (10 microM)] receptor antagonists or by tetrodotoxin (TTX) at concentrations of 1 or 3 microM. The phase response curve for heat pulses is similar to ones obtained with light pulses for behavioral rhythms. These data demonstrate that circadian pacemaker period in the rat SCN is temperature-compensated over a physiological range of temperatures. Phase delays were not caused by activation of ionotropic glutamate receptors, release of other neurotransmitters, or temperature-dependent increases in metabolism associated with action potentials. Heat pulses may have phase-shifted rhythms by directly altering transcriptional or translational events in SCN pacemaker cells.

Phase shift magnitude and direction determine whether Siberian hamsters reentrain to the photocycle.

Body temperature (Tb) or activity rhythms were monitored in male Siberian hamsters (Phodopus sungorus) housed in an LD cycle of 16 h light/day from birth. At 3 months of age, rhythms were monitored for 14 days, and then the LD cycle was phase delayed by 1, 3, or 5 h or phase advanced by 5 h in four separate groups of animals. Phase delays were accomplished via a 1- or 3-h extension of the light phase or via a 5-h extension of the dark phase. The phase advance was accomplished via a 5-h shortening of the light phase. After 2 to 3 weeks, hamsters that were phase delayed by 1 or 3 h were then phase advanced by 1 or 3 h, respectively, via a shortening of the light phase. All of the animals reentrained to phase delays of 1 or 3 h and to a 1-h phase advance; 79% reentrained to a 3-h phase advance. In contrast, only 13% of the animals reentrained to the 5-h phase advance, 13% became arrhythmic, and 74% free ran for several weeks. After the 5-h phase delay, however, reentrainment was observed in 50% of the animals although half of them required more than 21 days to reentrain. The response to a phase shift could not be predicted by any parameter of circadian rhythm organization assessed prior to the phase shift. These data demonstrate that a phase shift of the LD cycle can permanently disrupt entrainment mechanisms and eliminate circadian Tb and activity rhythms. Magnitude and direction of a phase shift of the LD cycle determine not only the rate but also the probability of reentrainment. Furthermore, the phase of the LD cycle at which the phase shift is made has a marked effect on the proportion of animals that reentrain. Light exposure during mid-subjective night combined with daily light exposure during the active phase may explain these phenomena.

Suprachiasmatic nucleus: role in circannual body mass and hibernation rhythms of ground squirrels.

Female golden-mantled ground squirrels that sustained complete ablation of the suprachiasmatic nucleus (SCNx) were housed pre- and post-operatively at 23 degrees C and then at 6.5 degrees C for 5-7 yr. SCNx and control animals held at the higher temperature manifested circannual rhythms (CARs) in body mass. In contrast, body mass CARs were not expressed in 50% of SCNx squirrels during cold exposure; rhythm amplitude was reduced to 25-40% of pre-operative values and the interval between successive peaks in body mass fell outside the circannual range. Unlike normal squirrels that hibernate for about 6 months during each circannual cycle, these SCNx squirrels expressed bouts of torpor nearly continuously throughout 2.5 yr of cold exposure. Body mass increases were often observed during hibernation--a phenomenon never observed in control animals. The remaining SCNx squirrels that did not hibernate continuously displayed CARs in body mass within the normal range. The effects of SCN ablation on body mass rhythms presumably are related to disrupted patterns of hibernation, food intake, and metabolism. The SCN, which sustains neural and metabolic activity at low tissue temperatures, may exert greater influence on thermoregulation and metabolism during the hibernation season than at other times of year, thereby accounting for the greater effect of SCN ablation in squirrels maintained at low ambient temperatures.

The aged suprachiasmatic nucleus is phase-shifted by cAMP in vitro.

The cyclic adenosine monophosphate (cAMP) analog, 8-bromo-cAMP, phase advanced circadian neuronal rhythms in both aged and adult rat suprachiasmatic nuclei (SCN) by approximately 2 h in vitro. Rhythm amplitude was 20% lower in aged compared to adult SCN. The diminished efficacy of serotonergic agonists to phase shift behavioral rhythms of aged animals may be due to decrements in signal transduction mechanisms proximal to cAMP.

Melatonin attenuates photic disruption of circadian rhythms in Siberian hamsters.

Body temperature (Tb) was recorded via a biotelemetry system from 28 adult male Siberian hamsters maintained in a light-dark (LD) cycle of 16 h light/day for several months. After Tb was recorded for 3 wk, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8 LD cycle for the remainder of the experiment. Hamsters were injected daily with melatonin or vehicle solution for several weeks, beginning either 2 mo after (experiment 1) or on the day of (experiment 2) the phase shift; injections occurred within 30 min of dark onset. In experiment 1, 75% of animals free ran with circadian periods >24 h, beginning on the day of the phase shift, and never reentrained to the LD cycle; no hamsters unambiguously entrained to daily injections. In contrast, 78% of animals in experiment 2 entrained to melatonin injections, and 71% of those animals subsequently reentrained to the photocycle when the injection regimen ended. No vehicle-treated animals entrained to the injection schedule. Melatonin had no effect on daily mean Tb and Tb rhythm amplitude in either experiment; however, melatonin doubled the duration of a hyperthermic response that occurred after each injection. Thus melatonin can prevent loss of entrainment induced by a phase shift of the LD cycle but cannot restore entrainment to free-running animals. Failure to reentrain in the presence of two appropriately coordinated entraining agents also suggests that a phase shift of the photocycle can diminish the sensitivity of the circadian system to both photic and nonphotic input.

Siberian hamsters free run or become arrhythmic after a phase delay of the photocycle.

Body temperature (Tb) and locomotor activity were recorded telemetrically from male Siberian hamsters (Phodopus sungorus sungorus) that were 3 or 12 mo of age and maintained in a light-dark (LD) cycle of 16 h light/day for 2-4 mo. After 3 wk of Tb recording, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8-h LD cycle for the remainder of the experiment. Tb and activity rhythms of all animals were stably entrained to the LD cycle before the phase shift. After the phase shift, > or = 80% of the animals in each age group failed to reentrain and expressed free-running Tb rhythms with stable periods that ranged from 24.33 to 26.33 h; one hamster in each age group reentrained within several days. Tb became arrhythmic in 10% of all animals immediately after, and in 28% of free running animals several weeks after, the phase shift. Changes in tau and phase of activity rhythms closely paralleled Tb rhythms in individual hamsters. Daily mean Tb was unchanged, but Tb rhythm amplitude decreased by 25-50% in individual animals after the phase shift. We believe this to be the first report of neurologically intact animals failing to reentrain to a phase shift of the LD cycle. These phenomena are not readily explained by current knowledge of circadian systems and suggest that the entrainment process in Siberian hamsters differs markedly from that in other rodent species.

Ablation of suprachiasmatic nucleus alters timing of hibernation in ground squirrels.

Hibernation patterns were monitored continuously for 2.5 years in female squirrels that were neurologically intact or in which the hypothalamic suprachiasmatic nucleus (SCN) was completely ablated (SCNx). The number of hibernation bouts in SCNx squirrels increased by 159%, total hibernation time increased by 58%, and periodic arousals from hibernation were 47% longer in SCNx than in control squirrels; the duration of individual torpor bouts was 2 days shorter and far more variable in SCNx than in control animals. Some SCNx squirrels cycled through bouts of torpor continuously for nearly 2 years. The SCN appears to be part of the mechanism that controls the duration of the hibernation season and the temporal structure of individual torpor bouts.

Temperature sensitivity of the suprachiasmatic nucleus of ground squirrels and rats in vitro.

Temperature compensation of circadian rhythms in neuronal firing rate was investigated in the suprachiasmatic nucleus (SCN) of ground squirrels and rats in vitro. A reduction in SCN temperature from 37 to 25 degrees C reduced peak firing rates by > 70% in rats but only by approximately 21% in squirrels; trough firing rates were marginally altered in both species. In the rat SCN at 25 degrees C, the peak in neuronal activity decreased progressively on successive days and circadian rhythms no longer were present by Day 3. There was a 37% reduction in the number of single units detected and an increase in the temporal variability of peak firing rates among individual rat SCN neurons at low temperature. By contrast, single units were readily detected and circadian rhythms were robust in squirrels at 37 and 25 degrees C; a Q10 of 0.927 was associated with a shortening of tau by 2 h and a 5-h phase change after only 48 h at low temperature. These results suggest that temperature can have a substantial impact on circadian organization in a mammalian pacemaker considered to be temperature compensated.

Paraventricular nucleus ablation disrupts daily torpor in Siberian hamsters.

Siberian hamsters were maintained in a short-day photoperiod (8 h light/day) at 15 degrees C; body temperature (Tb) was telemetrically monitored at 10-min intervals over the course of 4 months. Animals manifesting repeated torpor bouts (Tb < 30 degrees C) were subjected to lesions of the paraventricular nucleus (PVN) or a sham operation. In the 8 weeks after surgery, 67% of the animals with complete bilateral ablation of the PVN failed to express torpor; circadian Tb rhythms, as determined by periodogram analysis, were normal in all operated and sham-operated animals. Body mass did not change in PVN-ablated animals that continued to express torpor; in contrast, rapid and sustained increases in body mass were manifested by all hamsters that terminated expression of torpor. Expression of torpor is attenuated in the absence of the PVN; it is suggested that the PVN influences torpor indirectly by regulating body mass or the availability of metabolic fuels.

Olfactory bulb removal lengthens the period of circannual rhythms and disrupts hibernation in golden-mantled ground squirrels.

Removal of the olfactory bulbs lengthened the period of circannual rhythms (CARs) of body mass and plasma testosterone (T) concentrations in male golden-mantled ground squirrels, but did not otherwise alter their expression. The period of the CAR was approximately 2 months longer in bulbectomized than in sham-operated animals. Peak values of body mass and T were unaffected by bulbectomy. All neurologically intact, but only 50% of bulbectomized, squirrels displayed normal hibernation patterns. We conclude that the olfactory bulbs are not the site of essential circannual oscillators. Circannual reproductive and hibernation cycles of ground squirrels are less subject to modulation by the olfactory bulbs than are the corresponding rhythms of several non-circannual hamster species.

Prolactin and testosterone inhibit torpor in Siberian hamsters.

Female Siberian hamsters maintained in a winter photoperiod (8 h light/day) ceased to undergo daily torpor during infusion of prolactin (PRL) from osmotic minipumps; winter torpor was reinstated within 3 days of discontinuation of treatment. By contrast, PRL infusion was ineffective in suppressing daily torpor elicited by restricting food intake in female hamsters housed in a summer photoperiod (16 h light/day). Summer daily torpor was, however, completely inhibited in long-day gonadectomized male hamsters treated with testosterone (T). We suggest that the hyperprolactinemia, which in previous studies is characteristic of hamsters that sustain ablation of the suprachiasmatic nucleus, is incompatible with winter torpor. Summer torpor may be controlled by a mechanism less responsive to variations in plasma PRL concentration. Both winter and summer torpor are inhibited by exogenous T; it remains uncertain, however, whether sustained decreases in endogenous T secretion are as essential for the expression of summer as they are for winter torpor.

Daily torpor in the absence of the suprachiasmatic nucleus in Siberian hamsters.

Siberian hamsters express torpor spontaneously after several weeks of exposure to short days. In long days, torpor is expressed only when food intake is restricted. Hamsters maintained in a long photoperiod (16 h light/day) at 15 degrees C expressed daily torpor during food restriction both before and after bilateral ablation of the suprachiasmatic nucleus (SCN). Hamsters housed in short days (8 h light/day, ambient temperature 15 degrees C) and fed ad libitum displayed torpor before, but not after, ablation of the SCN (SCNX). Torpor was reinstated in all short-day SCNX hamsters during postoperative food restriction and persisted in several animals even after ad libitum feeding was reinstated. Torpor was entrained to the light-dark cycle in both long- and short-day hamsters preoperatively but appeared to occur in a temporally random fashion in SCNX animals. SCNX hamsters, unlike control animals, displayed multiple torpor bouts per 24 h. The SCN is not essential for the expression of torpor but plays a crucial role in its temporal organization.

Accelerated reproductive development in juvenile male ground squirrels fed a high-fat diet.

Male golden-mantled ground squirrels held at 23 degrees C were fed high-fat (HF) or standard (chow) diets. In December, ambient temperature was reduced to 6 degrees C, food was removed, and frequency and duration of torpor bouts were monitored continuously by radiotelemetry. Reproductive condition and body composition were assessed upon terminal arousal in the spring. Juvenile males fed the HF diet weighed more than chow-fed controls before and throughout the hibernation season and had significantly greater lipid masses at terminal arousal. Testes masses and plasma testosterone concentrations were substantially higher in HF than in chow-fed juveniles. The accelerated reproductive development of fatter squirrels was not contingent upon increases in the total number of days spent in torpor, number of torpor bouts, or the average duration of each arousal from torpor. Access to the HF diet had no effect on body mass, adiposity, or reproductive status of adult male ground squirrels in spring. Threshold levels of white adipose tissue and associated differences in availability of metabolic fuels may be permissive for testicular growth during the hibernation season. Juveniles exceed this threshold only when fed the HF diet.

Suprachiasmatic nuclei influence torpor and circadian temperature rhythms in hamsters.

Siberian hamsters were maintained in a short-day photoperiod (8 h light-day) at 15 degrees C; body temperature (Tb) and locomotor activity were telemetrically recorded at 10-min intervals over the course of 5 mo. Animals manifesting repeated torpor bouts (Tb less than 30 degrees C for several hours) were subjected to lesions of the suprachiasmatic nuclei (SCN), pinealectomy, or sham operations. In the 15 wk after surgery, none of the animals with bilateral lesions of the SCN exhibited torpor; circadian Tb and locomotor activity rhythms, as determined by cosinor and power spectral analysis, also were absent in SCN-lesioned hamsters. Pinealectomized animals and brain-lesioned hamsters with intact SCN had normal circadian temperature and activity rhythms and showed torpor for at least 4 wk postsurgically. Expression of torpor and circadian rhythms of Tb and activity are dependent on intact SCN and persist for several weeks in the absence of pineal secretory activity.

Dietary obesity in exercising or cold-exposed Syrian hamsters.

High-fat diet-feeding increases body weight and adiposity in Syrian hamsters (Mesocricetus auratus), effects due in part to decreased energy expenditure. The effects of voluntary exercise- or cold exposure-induced increases in energy expenditure were examined in fat- or chow-fed, female Syrian hamsters. In Experiment 1, voluntary exercise (10 weeks) caused a moderate hyperphagia and actually increased body weight in both diet groups through increases in lean body mass. Carcass lipid was not affected by by exercise in chow-fed hamsters and only slightly reduced in fat-fed animals. In Experiment 2, chronic (8 weeks) cold exposure (5 degrees C) increased energy intake to the same extent in both dietary groups relative to the warm-exposed (23 degrees C) controls. High-fat diet-induced obesity was largely prevented by cold exposure. Cold exposure reduced lean body mass in chow-fed hamsters, but this carcass component was spared by fat-feeding. These results indicate that the increased metabolic demands of cold exposure were more effective in preventing this form of diet-induced obesity than those of voluntary exercise (80% and 17% reductions in carcass lipid, respectively). These results are discussed in terms of possible beneficial effects of eating a lipid-rich diet prior to winter.