Behavioural Brain Research 168 (2006) 56–63 Research report C-section birth per se or followed by acute global asphyxia altered emotional behaviour in neonate and adult rats Aldina Venerosi, Debora Cutuli, Flavia Chiarotti, Gemma Calamandrei ∗ Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanit` a, Viale Regina Elena 299, I-00161 Rome, Italy Received 16 September 2005; received in revised form 14 October 2005; accepted 18 October 2005 Available online 28 November 2005 Abstract Birth complications such as perinatal asphyxia are considered risk factors for later neurobehavioural disorders. Behavioural analysis of animal models may help to clarify the contribution of particular patterns of early hypoxia and their combination to psychiatric morbidity. Wistar rats underwent caesarean section (c-section) alone or c-section followed by asphyxia, the latter induced by placing pups still in uterus horns into a water bath at 37 ◦ C for 20min. Vaginally delivered pups were used as controls. Frequency of ultrasound emissions was analysed following isolation at a lower temperature than that of the home nest (23 ± 0.5 ◦ C) and reunion with their mother (3 min) on postnatal day (PND) 13 (maternal potentiation test). A sex-dependent effect of hypoxia was observed, with higher production of ultrasounds in hypoxic males. Caesarean-delivered pups produced significantly more ultrasounds than those vaginally delivered. At adolescence (PND 35) rats underwent a 25 min social interaction test with a conspecific of the same sex and age. Significant alterations in investigative behaviour (inclusive of: nose, anogenital, body sniffing, and following) were evident in caesarean-delivered rats of both sexes, but not in rats experiencing perinatal asphyxia. At adulthood, auditory, and context conditioned responses, analysed in a fear conditioning test, were not markedly affected either by c-section or c-section plus hypoxia. However, hypoxic rats emitted significantly more 22kHz ultrasounds than c-section or vaginally delivered rats during the training session. In conclusion, differential effects appear to be brought about by c-section and by hypoxia mainly related to emotional/anxious responses. © 2005 Elsevier B.V. All rights reserved. Keywords: Perinatal asphyxia; Caesarean birth; Ultrasound vocalisation; Social behaviour; Fear conditioning; Rat 1. Introduction Obstetric complications and in particular foetal and perina- tal asphyxia have been associated with the onset of neurobe- havioural and neuropsychiatric pathologies such as attention deficit hyperactivity disorder (ADHD), autism or schizophre- nia [18,19,48,53]. In a recent historical meta-analytic review, Cannon et al. [13] reported that among obstetric complications, alongside asphyxia, emergency caesarean section was signifi- cantly associated with schizophrenia. Though conclusive data are still lacking on a direct causal link between schizophrenia and complications of labour and delivery, hypoxia at birth is likely to play a role in increasing vulnerability to a wide spec- trum of neurodevelopmental disorders. The damage produced by asphyxia is almost proportional to the duration and severity of the ∗ Corresponding author. Tel.: +39 06 49902106; fax: +30 06 4957821. E-mail address: gemma.calamandrei@iss.it (G. Calamandrei). hypoxic episode, inducing true encephalopathy with moderate or severe neonatal symptoms [49], or mild or absent pathological signs at birth, which might become evident later in life [2,44]. It is namely in the latter condition that subtle insults – target- ing selectively structure and/or maturational CNS processes – could interact with individual factors such as environmental and genetic vulnerability favouring later development of CNS dis- order [13,32,43,59]. In such context, the use of animal models of birth complica- tions may help to clarify the relative contribution of particular patterns of early hypoxia, and their combination, to changes in brain and behaviour functioning, that may predispose to neu- robehavioural disorders of varying degree of severity. Several studies have been carried out on a rodent model of global peri- natal hypoxia [3] in order to elucidate the consequences of early hypoxic insult on CNS functioning [21]. This model, exposing foetuses in utero to global asphyxia after c-section, appears to mimic properly human complications at birth, where the entire organism is involved in the hypoxic condition as well as in 0166-4328/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2005.10.010