Cold exposure and sleep in the rat: REM sleep homeostasis and body size.

STUDY OBJECTIVES: Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24 degrees C. DESIGN: EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10 degrees C to -10 degrees C and for 4 days during recovery. SETTING: Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. SUBJECTS: 24 male albino rats. INTERVENTIONS: Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. MEASUREMENTS AND RESULTS: REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a "fast rebound" threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery. CONCLUSION: Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation.

Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat.

In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas. The results showed that DP delivery triggers a transition from NREMS to REMS comparable to that which occurs spontaneously. However, the efficiency of DP delivery in inducing REMS was reduced during cold exposure to an extent comparable with that observed in spontaneous REMS occurrence. Such impairment was associated with low Delta activity and high sympathetic tone when DPs were delivered. Repetitive DP administration increased REMS amount during the delivery period and a subsequent negative REMS rebound was observed. In conclusion, DP delivery did not overcome the integrative thermoregulatory mechanisms that depress REMS in the cold. These results underline the crucial physiological meaning of the mutual exclusion of thermoregulatory activation and REMS occurrence, and support the hypothesis that the suspension of the central control of body temperature is a prerequisite for REMS occurrence.

Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat.

The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (T(a)). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T(a); (iv) a significant increase of IP(3) concentration in CC following exposure to low T(a). The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.

Changes in EEG activity and hypothalamic temperature as indices for non-REM sleep to REM sleep transitions.

A shift of physiological regulations from a homeostatic to a non-homeostatic modality characterizes the passage from non-NREM sleep (NREMS) to REM sleep (REMS). In the rat, an EEG index which allows the automatic scoring of transitions from NREMS to REMS has been proposed: the NREMS to REMS transition indicator value, NIV [J.H. Benington et al., Sleep 17 (1994) 28-36]. However, such transitions are not always followed by a REMS episode, but are often followed by an awakening. In the present study, the relationship between changes in EEG activity and hypothalamic temperature (Thy), taken as an index of autonomic activity, was studied within a window consisting of the 60s which precedes a state change from a consolidated NREMS episode. Furthermore, the probability that a transition would lead to REMS or wake was analysed. The results showed that, within this time window, both a modified NIV (NIV(60)) and the difference between Thy at the limits of the window (Thy(D)) were related to the probability of REMS onset. Both the relationship between the indices and the probability of REMS onset was sigmoid, the latter of which saturated at a probability level around 50-60%. The efficacy for the prediction of successful transitions from NREMS to REMS found using Thy(D) as an index supports the view that such a transition is a dynamic process where the physiological risk to enter REMS is weighted at a central level.

Cold exposure and sleep in the rat: effects on sleep architecture and the electroencephalogram.

STUDY OBJECTIVES: Acute exposure to low ambient temperature modifies the wake-sleep cycle due to stage-dependent changes in the capacity to regulate body temperature. This study was carried out to make a systematic analysis of sleep parameters during the exposure to different low ambient temperatures and during the following recoveries at ambient temperature 24 degrees C. DESIGN: Electroencephalographic activity, hypothalamic temperature, and motor activity were studied during a 24-hour exposure to ambient temperatures ranging from 10 degrees C to -10 degrees C and for 4 days during the recovery. SETTING: Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. SUBJECTS: Twenty-four male albino rats. INTERVENTIONS: Animals were implanted with electrodes for electroencephalographic recording and a thermistor for measuring hypothalamic temperature. MEASUREMENTS AND RESULTS: Wake-sleep stage duration and the electroencephalographic spectral analysis performed by fast Fourier transform were compared among baseline, exposure, and recovery conditions. The amount of non-rapid eye movement sleep was slightly depressed by cold exposure, but no rebound was observed during the recovery period. Delta power during non-rapid eye movement sleep was decreased in animals exposed to the lowest ambient temperatures and increased during the first day of the recovery. In contrast, rapid eye movement sleep was greatly depressed by cold exposure and showed an increase during the recovery. Both of these effects were dependent on the ambient temperature of the exposure. Moreover, theta power was increased during rapid eye movement sleep in both the exposure and the first day of the recovery. CONCLUSION: These findings show that sleep-stage duration and electroencephalogram power are simultaneously affected by cold exposure. The effects on rapid eye movement sleep appear mainly as changes in the duration, whereas those on non-rapid eye movement sleep are shown by changes in delta power. These effects are temperature dependent, and the decrease of both parameters during the exposure is reciprocated by an increase in the subsequent recovery.

Specific changes in cerebral second messenger accumulation underline REM sleep inhibition induced by the exposure to low ambient temperature.

In the rat the exposure to an ambient temperature (Ta) of -10 degrees C induces an almost total REM sleep deprivation that results in a proportional rebound in the following recovery at normal laboratory Ta when the exposure lasts for 24 h, but in a rebound much lower than expected when the exposure lasts 48 h. The possibility that this may be related to plastic changes in the nervous structures involved in the control of thermoregulation and REM sleep has been investigated by measuring changes in the concentration of adenosine 3':5'-cyclic monophosphate (cAMP) and D-myo-inositol 1,4,5-trisphosphate (IP(3)) in the preoptic-anterior hypothalamic area (PO-AH), the ventromedial hypothalamic nucleus (VMH) and, as a control, the cerebral cortex (CC). Second messenger concentration was determined in animals either stimulated by being exposed to hypoxia, a depolarizing condition that induces maximal second messenger accumulation or unstimulated, at the end of a 24-h and a 48-h exposure to -10 degrees C and also between 4 h 15 min and 4 h 30 min into recovery (early recovery). At the end of both exposure conditions, cAMP concentration significantly decreased in PO-AH-VMH, but did not change in CC, whilst changes in IP(3) concentration were similar in all these regions. The low cAMP concentration in PO-AH-VMH was concomitant with a significantly low accumulation in hypoxia. The normal capacity of cAMP accumulation was only restored in the early recovery following 24 h of exposure, but not following 48 h of exposure, suggesting that this may be a biochemical equivalent of the REM sleep inhibition observed during 48 h of exposure and which is carried over to the recovery.