Available online at www.sciencedirect.com Behavioural Brain Research 189 (2008) 373–380 Research report Intermittent hypoxia and sleep restriction: Motor, cognitive and neurochemical alterations in rats Juliana C. Perry a,∗ , Vˆ ania D’Almeida a,b , Marcelo M.S. Lima a , Francisco R.L. Godoi a , Maria Aparecida B.F. Vital c , Maria Gabriela M. Oliveira a , Sergio Tufik a a Department of Psychobiology, Universidade Federal de S˜ ao Paulo, S˜ ao Paulo, Brazil b Department of Biosciences, Universidade Federal de S˜ ao Paulo, S˜ ao Paulo, Brazil c Department of Pharmacology, Universidade Federal do Paran´ a, Curitiba, Brazil Received 28 June 2007; received in revised form 23 January 2008; accepted 28 January 2008 Available online 5 February 2008 Abstract The present study evaluated the effects of intermittent hypoxia (IH) and sleep restriction (SR) upon motor and cognitive function in rats. Also evaluated were catecholamine concentrations and tyrosine hydroxylase (TH) protein expression in different regions of the forebrain. Wistar Hannover rats were submitted to IH for 4 days or 21 days (2 min room air to 2 min 10% O 2 for 10:00–16:00 h), followed by SR for 18 h (16:00–10:00 h). Rats were randomly assigned into four experimental groups: (1) control (2) IH (3) SR and (4) IH–SR. In the inhibitory avoidance task, an additional group of rats was submitted to paradoxical sleep deprivation (PSD) for 96 consecutive hours. Results showed that SR induced an increase in motor activity without modifying catecholaminergic turnover in the frontal cortex and striatum. The increase in exploratory activity in SR rats could be the result of impaired habituation. Neither SR periods induced cognitive deficits in the inhibitory avoidance task after 5 or 21 days. However, 96h of PSD impaired acquisition/retention in rats. Exposure to IH did not affect motor and cognitive function but IH was associated with SR in increased motor activity. After 21 days, IH and IH–SR reduced striatal norepinephrine concentration although neither SR nor IH affected TH protein expression. The results presented here suggest that hypoxia and sleep loss exert distinct deleterious effects upon the central nervous system. © 2008 Elsevier B.V. All rights reserved. Keywords: Hypoxia; Sleep deprivation; Motor; Memory; Norepinephrine; Rat 1. Introduction Obstructive sleep apnea is characterized by repetitive obstruction of the upper airways resulting in pauses in breathing and subsequent oxygen desaturation. These alterations lead to arousals commonly associated with hypoxia and consequently lead to sleep deprivation. The classic daytime manifestation of apnea is excessive sleepiness but other symptoms such as cog- nitive deficits and fatigue are commonly reported [33]. Several neurobehavioral morbidities with major impact on public health and the economy may be related to obstructive sleep apnea. More direct effects are seen in traffic and workplace accidents [13,14,29]. ∗ Corresponding author at: Department of Psychobiology, Universidade Fed- eral de S˜ ao Paulo, Rua Napole˜ ao de Barros, 925, Vila Clementino - SP - 04024-002, S˜ ao Paulo, Brazil. Tel.: +55 11 2149 0155; fax: +55 11 5572 5092. E-mail address: jperry@psicobio.epm.br (J.C. Perry). Both hypoxia and sleep deprivation have been suggested to be contributors to cognitive deficits observed in apnea patients [6]. Gozal’s group demonstrated that exposure to intermittent hypoxia (IH) is associated with impairment of spatial learning in adult rats and increased apoptosis in the cortex and CA 1 region of the hippocampus [16]. Moreover, IH exposure during the devel- opment of the nervous system (7–11 days of age) induced deficits in spatial working memory in juvenile rats [9]. When hypoxia occurs during a critical period of brain development, a short- age of oxygen in the brain disrupts the functional integrity of the dopaminergic system and induces motor alterations [9,10]. Exposure to IH in adult rats has been associated with the mod- ified biosynthesis of both norepinephrine and dopamine in the brain [24,31]. Studies have demonstrated that 96 h of paradoxical sleep deprivation (PSD) impairs attention [15] and acquisition/ retention of an aversive task [8,32]. PSD can lead to behav- ioral alterations, some of which have been attributed to 0166-4328/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2008.01.014