Behavioural Brain Research 154 (2004) 549–555 Research report Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats Thomas H.J. Burne a,∗ , Axel Becker b , Jillanne Brown d , Darryl W. Eyles c,d , Alan Mackay-Sim a , John J. McGrath c,e a Centre for Molecular Neurobiology, School of Biomolecular and Biomedical Science, Griffith University, Brisbane, Qld 4111, Australia b Institute of Pharmacology and Toxicology, Faculty of Medicine, Otto-von-Guericke-University, Leipziger Str. 44, 39120 Magdeburg, Germany c Queensland Centre for Schizophrenia Research, The Park Centre for Mental Health, Wacol, Qld 4076, Australia d Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Qld 4072, Australia e Department of Psychiatry, The University of Queensland, Brisbane, Qld 4072, Australia Received 12 December 2003; received in revised form 24 March 2004; accepted 25 March 2004 Available online 27 April 2004 Abstract Rat experiments have shown that prenatal Vitamin D deficiency leads to altered neonatal brain morphology, cell density and neurotrophin expression. In the current study we examined the hypothesis that Vitamin D deficiency during early development alters adult behaviour even when there is an intervening period in which the animal receives normal Vitamin D in later development. Rats were conceived and born to Vitamin D deficient dams (Birth); conceived, born and weaned from Vitamin D deficient dams (Weaning); or deficient in Vitamin D from conception to 10 weeks of age (Life). Litters were standardized to three males and three females per litter. All rat offspring were rendered normocalcaemic with calcium supplemented water (2 mM) after weaning. Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks all animals were tested on the holeboard test, elevated plus maze test, social interaction observation, acoustic startle response test, prepulse inhibition of the acoustic startle response and a forced swim test. Early Vitamin D deficiency (Birth group) enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, transient prenatal Vitamin D deficiency induces hyperlocomotion in adulthood, without severe motor abnormalities. © 2004 Elsevier B.V. All rights reserved. Keywords: Locomotor activity; Elevated plus maze; Social interaction; Swim test; Acoustic startle; Development; Sprague–Dawley rats; Prepulse inhibition; Vitamin D 1. Introduction Vitamin D 3 (Calcitriol, 1,25-dihydroxyvitamin D 3 ) is now thought to be involved in brain function as well as in the reg- ulation of calcium and phosphate homeostatis and in bone formation [12]. For example, there is a dense distribution of the Vitamin D receptor (VDR) in rat brain throughout development and into adulthood [23,27]. However, the role Vitamin D and its receptor (VDR) play in the brain are un- clear. Recent evidence suggests that Vitamin D is involved with the biosynthesis of neurotrophic factors, regulation of neurotransmitters and detoxification pathways [12]. In addi- tion Vitamin D has been shown to have neuroprotective and immunomodulatory effects [3,5,6]. ∗ Corresponding author. Tel.: +61-7-38756482; fax: +61-7-38757773. E-mailaddress: t.burne@griffith.edu.au (T.H.J. Burne). Recently our group demonstrated that prenatal Vitamin D deficiency has profound effects on brain development [9]. For example, neonatal rats born to Vitamin D deplete dams have enlarged ventricles, a thinner cortex and increased cell proliferation, as wellas reductions in nerve growth factor (NGF),glialcellline-derived growth factor (GDNF)and the low affinity neurotrophin receptor, p75 [9].Further- more, transient prenatal Vitamin D deficiency has also been shown to cause persistent changes in ventricle size and NGF expression in adult rats [10]. In lightof the changes found in the brains of newborn pups exposed to prena- talhypovitaminosis D, we were interested in exploring if these animals had altered behaviour as adults. We showed recently that rats with combined prenatal and chronic post- natalVitamin D deficiency had impaired prepulse inhibi- tion (PPI) despite having normal acoustic startle responses [4]. However, as these animals were also hypocalcaemic 0166-4328/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2004.03.023