Sleep deprivation elevates plasma corticosterone levels in neonatal rats Ilana S. Hairston a,b, * , Norman F. Ruby b , Sheila Brooke b , Christelle Peyron b , Daniel P. Denning b , H. Craig Heller a,b , Robert M. Sapolsky a,b a Neurosciences Program, School of Medicine, Stanford University, Stanford, CA, USA b The Department of Biological Sciences, Stanford University, Stanford, CA, USA Received 3 August 2001; received in revised form 18 September 2001; accepted 18 September 2001 Abstract 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. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Sleep deprivation; Corticosterone; Development; Stress; Neonatal rats; Stress-hyporesponsive period Sleep deprivation is often perceived as a stressful experi- ence. Activation of the hypothalamic-pituitary-adrenal (HPA) axis, which results in secretion of species-specific glucocorticoids (e.g. corticosterone (CORT) in rats, cortisol in humans), corticotrophin-releasing hormone, and adreno- corticotrophic hormone, is the physiological marker of stress in mammals (i.e. the stress-response, [15]). Observa- tions that sleep deprivation results in an increase in plasma glucocorticoids in both humans [17] and rodents [1,18], support the conjecture that sleep loss is a physiological stressor. Moreover, stress-related hormones have complex effects on the amount and quality of sleep after a variety of stressful experiences [9,12] and after sleep deprivation [10], which suggests that the HPA axis may be involved in the regulation of sleep. In young mammals the stress response is attenuated. Neonatal rats, 2–14 days of age, have low basal levels of CORT and a diminished capacity to increase CORT levels in response to a stressor [16]. This age window is termed the stress hyporesponsive period. Exposure to CORT has adverse effects on the nervous system such as suppressing neurogenesis and the formation of neural networks [5,13]. Therefore the stress hyporesponsive period is perceived as a mechanism for protecting the developing nervous system at this age [15]. Nevertheless, severe manipulations, such as prolonged maternal separation or physical trauma result in elevated levels of CORT [13]. It was thus of interest to test whether sleep depriving young rats, less than 1 month of age, would increase CORT levels. Based on the above we predicted that sleep deprivation would elevate CORT levels only in rats older than 14 days of age. Long–Evans rats were bred in the lab and maintained on a 12:12 light/dark cycle, at an ambient temperature of 228C. Food and water were available ad libitum. Day of birth was designated postnatal day 0 (P0). Litter size ranged from 8–12 pups. Surgery, recording, and sleep deprivation procedures were performed as previously described [8]. At P9, three male and three female pups per litter were anaesthetized with methoxyflurane inhalant (Metofane, Mallinckrodt Veterinary, Australia). Four EEG electrodes (no. 000 stain- less steel screws) were fastened bilaterally in frontal and parietal bones. Three EMG electrodes (stainless steel wire) were inserted into the nuchal muscles. All electrodes were attached to a seven-pin electric socket that was fastened to the skull with dental acrylic and the incision was sutured. After Neuroscience Letters 315 (2001) 29–32 0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(01)02309-6 www.elsevier.com/locate/neulet * Corresponding author. Department of Biological Sciences, Stanford University, Gilbert Building, 371 Serra Mall, Stanford, CA 94305-5020, USA. Tel.: 11-650-7235882; fax: 11-650-7255356. E-mail address: Ilana.Hairston@stanford.edu (I.S. Hairston).