Research reportDifferential effects of acute cold and footshock on the sleep of rats
Introduction
Sleep, as any behaviour, is affected by several kinds of disturbances, such as stress. According to Opp [27], sleep patterning may be a useful response marker for a variety of stimuli for two reasons. First, it is based in established criteria and is well defined and quantifiable. Second, sleep represents the summation of multiple systems that may be differentially altered by stress. Thus, the degree by which the sleep–wake cycle is modified by a specific stressor may be an indicator of the magnitude of such stressor as well as the activation of the hypothalamic-pituitary-adrenal (HPA) axis.
The influence of stress on sleep has been the focus of a number of studies, both in humans and in laboratory animals. Stress has been associated to anxiety and depression [3]. In a recent survey, 95% of depressive and anxious patients reported sleep problems; insomnia was the most frequent complaint [40]. Moreover, depressive patients present, simultaneously, high cortisol plasma levels and reduced latency to REM sleep and augmented time of REM sleep on the first half of the night, when there is a predominance of slow wave sleep (SWS) 2, 15, 33.
In animals, altered sleep patterning is observed in rats submitted to a 2-h immobilisation stress (during their active period). Four hours after the stressor, these animals present a 32% rebound of paradoxical sleep (PS), without rebound of SWS [30]. If, however, the animals were submitted to 1 h of immobilisation, a 63% PS rebound and a 16% SWS rebound were observed [5]. Interestingly, repeated exposures to immobilisation lead to a progressive reduction of sleep rebound compared to single exposure [30]. A similar effect is observed following uncontrollable [21] and inescapable footshock [1], suggesting that habituation may take place 12, 34. Likewise, other stressors also influence sleep. Thus, exposure of animals to 1 h of social defeat results in 183.1% increase of the slow wave activity, suggesting that sleep may function as a compensation for the injuries to which the central nervous system is exposed during waking [24].
Data collected in other and our laboratories indicate that both physiological and behavioural responses to stress vary according to the stimuli. Thus, yawning is suppressed by constant prolonged exposure to stress, but not by prolonged intermittent exposure [38]. Similarly, sleep deprivation and isolation augment the activity of the immune system in an animal model of Lupus Erytemathosus, whereas immobilisation, footshock and swimming fail to induce any alteration [23]. Finally, 2 h of restraint stress results in down-regulation of 5-HT1a serotonergic receptors, whereas 15- or 30-min of swimming stress leads to the opposite effect [29].
In view of the somewhat differential effects of different stressors on neurotransmitter systems and organic responses, we sought to investigate the consequences of the acute exposure to several stressors on the sleep architecture of rats.
Section snippets
Subjects
Wistar male rats, 3 to 4 months old, weighing 300 to 430 g and raised in the animal facility of the Department of Psychobiology (UNIFESP-EPM) were used in this study. The animals were maintained in plastic cages, in groups of five, inside a room with controlled temperature (23±2°C) and 12-h light/12-h dark cycle (lights on at 0700 h). Food and water were available ad libitum throughout the study.
Stress procedures
(1) Immobilization: 10 animals were placed, individually, inside plastic cylinders (21×6 cm
ACTH levels
Due to the large variability within groups, data were converted to log and reanalysed (Fig. 1, upper panel). ANOVA revealed a difference among the groups [F(4,43)=52.57; P<0.0001]. Post hoc comparison showed that all stress groups presented a higher response than control (P<0.0001); footshock, however, induced the highest ACTH response (P<0.0002). Both immobilization and PS deprivation resulted in levels higher than cold (P<0.001), which in turn was higher than control values (P<0.01).
CORT levels
ANOVA
Discussion
The results of the present study showed that the stimuli employed produced a reliable activation of the HPA axis, with elevated plasma levels of ACTH and CORT. Nonetheless, these augmented responses, as well as the effect of the stimuli on the sleep architecture of rats occurred in a differential fashion.
Footshock was the only stressor that produced a state of prolonged alertness, with a reduction of TST and of sleep efficiency, and an elevation of TAT, whereas cold stress was the only one to
Acknowledgements
This work was supported by grants from Associação Fundo de Incentivo à Psicofarmacologia (AFIP) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Beatriz Duarte Palma and Deborah Suchecki are fellows from FAPESP, grants # 96/12545-4 and 9704857-9. The authors would like to thank Denise Zeminiani Theodoro and Tomé Pimentel dos Anjos for their valuable assistance in the hormone assays and blood sampling and to Jackson Cionek for technical support on the polysomnography equipment.
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