Behavioural Brain Research 163 (2005) 1–9 Research report Neonatal novelty exposure ameliorates anoxia-induced hyperactivity in the open field Akaysha C. Tang a,b,c,∗ , Masato Nakazawa a a Department of Psychology, University of New Mexico, Albuquerque, NM 87131, USA b Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA c Institute of Cognitive Neuroscience, University College London, 17 Queen Square, London WC1N 3AR, UK Received 17 November 2004; received in revised form 22 February 2005; accepted 24 March 2005 Available online 31 May 2005 Abstract We investigated in an animal model of neonatal anoxia whether effects of oxygen deprivation on emotional reactivity can be reversed by neonatal novelty exposure, a behavioral method, involving daily 3min away from the home cage for the first 3 weeks of life. Male neonates were exposed to either 100% N 2 gas (Anoxia) or room air (Control) for 25 min on postnatal day 1. Within each of the two treatment conditions, one-half of the neonates were further individually exposed to relatively novel non-home cages for 3min daily during postnatal days 2–21 (Novel: N Anoxia = 20; N Control = 16), while the other half remained in the home cage (Home: N Anoxia = 19; N Control = 19). Emotional reactivity to an open field was evaluated on postnatal day 25 during four 20-s trials. Among home rats, temporal patterns of open-field activity across multiple trials and initial-trial activity significantly differed between the Anoxia and Control rats. In contrast, these differences were eliminated among the Novel rats. These results show that neonatal novelty exposure, an early-stimulation method that has recently been shown to enhance spatial and social memory, adaptive control of stress response, and hippocampal synaptic plasticity, can also eliminate neonatal anoxia-induced changes in emotional reactivity. These findings suggest that brief and repeated, but mild, changes in the postnatal environment may serve to counteract some of the aversive effects induced by neonatal trauma associated with oxygen deprivation. © 2005 Elsevier B.V. All rights reserved. Keywords: Neonatal; Novelty; Anoxia; Open field; Emotional reactivity; Birth asphyxia; Stress; HPA axis; Corticosterone; Hyperactivity; Early intervention; Animal model 1. Introduction In humans, birth asphyxia, defined as impaired respira- tory gas exchange accompanied by the development of aci- dosis, occurs among 0.2–3% of live term births [19]. The single most consistent marker of an asphyxic event during the prenatal period is the evidence of neonatal encephalopa- thy, defined by a constellation of neurological signs observed within the first 7 days. Mild symptoms include increased ir- ritability, hyper-excitability, and sympathetic over-reactivity, ∗ Corresponding author at: Department of Psychology, University of New Mexico, Albuquerque, NM 87131, USA. Tel.: +44 20 7679 1135; fax: +44 20 7813 2835. E-mail address: akaysha@unm.edu (A.C. Tang). URL: http://atlab.unm.edu. while severe symptoms include coma, seizures, autonomic dysfunction, and brain stem dysfunction [19]. When these neurological signs occur as a result of asphyxia, it is often referred to as hypoxic–ischemic encephalopathy. Unfortu- nately, a majority of the clinical research deals with severe cases of neonatal encephalopathy and the outcome of asy- phyxiated infants in functional terms, such as socialization and daily living skills, has been insufficiently investigated [19]. This likely reflects a greater urgency in saving lives over the effort in improving quality of lives later on. One consequence of neonatal asphyxia that is likely to have long-lasting impact is behavioral hyperactivity. In an- imal models, anoxia/hypoxia has been shown to increase emotional reactivity to a novel environment as indexed by hyperactivity in the open-field test [2,12,26,41,54,64]. Sev- eral decades of infant temperament studies revealed that 0166-4328/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2005.03.025