Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids Slawomir Wojniusz a,b , Erik Ropstad c , Neil Evans d , Jane Robinson d , Anne-Kristin Solbakk a , Tor Endestad a,e , Ira Ronit Hebold Haraldsen a, * a Department of Neuropsychiatry and Psychosomatic Medicine, Division of Surgery and Clinical Neuroscience, Oslo University Hospital — Rikshospitalet, 0027 Oslo, Norway b Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pb 4 St. Olavsplass, 0130 Oslo, Norway c Norwegian School of Veterinary Science, Pb 8146 Dep, 0033 Oslo, Norway d Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 464 Beardsen Road, Glasgow G61 1QH, Scotland, UK e Institute of Psychology, University of Oslo, Pb 1094 Blindern, 0317 Oslo, Norway Received 8 October 2012; received in revised form 6 January 2013; accepted 4 February 2013 Psychoneuroendocrinology (2013) 38, 1709—1716 KEYWORDS Spatial orientation; Gonadotropin releasing hormone agonist; Gonadotropin releasing hormone; GnRH; Puberty; Sheep; Sex differences; Cognitive function Summary Prenatal exposure to androgens has been shown to modulate brain development, resulting in changed behavioral attitudes, sexual orientation and cognitive functions, including processing of spatial information. Whether later changes in gonadotropic hormones during puberty induce further organizational effects within the brain is still insufficiently understood. The purpose of this study was to assess development of spatial orientation before and after the time of normal pubertal development, in an ovine model where half of the animals did not undergo typical reproductive maturation due to the pharmacological blockade of gonadotropin releasing hormone receptor (GnRHR) signaling. The study formed part of a larger trial and utilized 46 pairs of same sex Scottish Mule Texel Cross twins (22 female and 24 male). One twin remained untreated throughout (control) while the other received a subcutaneous GnRH agonist (GnRHa: Goserelin-Acetate) implant every fourth week. GnRHa treatment began at eight and 28 weeks of age, in males and females respectively, because the timing of the pubertal transition is sexually differentiated in sheep as it is in humans. Spatial orientation was assessed at three different time points: eight weeks of age, before puberty and treatment in both sexes; 28 weeks of age, after 20 weeks GnRHa treatment in males and before puberty and GnRHa treatment in females; and at 48 weeks of age, which is after the normal time of the pubertal transition in both sexes. Spatial orientation was tested in a spatial maze with traverse time as the main outcome measure. GnRHa treatment did not affect spatial maze performance as no significant differences in traverse time between treated and untreated animals were observed at any time-point. * Corresponding author. Tel.: +47 92011533; fax: +47 23074930. E-mail address: i.h.haraldsen@medisin.uio.no (I.R.H. Haraldsen). Available online at www.sciencedirect.com j our na l h omepa g e: www.e lse vie r.c om/l oca te/ psyne ue n 0306-4530/$ — see front matter # 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psyneuen.2013.02.005