Diphenyl diselenide changes behavior in female pups Alexandre M. Favero, Simone N. Weis, Gilson Zeni, João B.T. Rocha, Cristina W. Nogueira ⁎ Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, SM, RS, CEP 97105-900 Santa Maria, Brazil Received 31 May 2006; received in revised form 5 August 2006; accepted 5 August 2006 Available online 15 August 2006 Abstract Diphenyl diselenide, (PhSe) 2 , is an organoselenium compound that affects a number of neuronal processes. The effect of maternal subcutaneous (s.c.) injection of 25 mg/kg (PhSe) 2 once daily during early postnatal development (from PND 1 to 21) was evaluated in offspring of Wistar rats. The physical and neural reflexes were recorded at pre-weaning period. The behavioral changes in the elevated plus-maze (EPM), open-field and rotarod tasks were performed in 28-day-old pups. Selenium brain status was significantly increased (∼ 41%) in rat pups. Statistically significant decreases in body weight were observed during lactation period in male and female pups exposed to 25 mg/kg (PhSe) 2 . There were no dose-related changes on landmarks indicative of physical and reflexologic parameters of development in rats. (PhSe) 2 induced a disinhibitory effect in EPM behavior according to gender. Specifically, exposure to (PhSe) 2 increased entries and duration in the open arms of the EPM in females but not in males. Locomotor activity and rearing increased by (PhSe) 2 exposure in both male and female offspring in the open field. Both groups were similar in response to motor coordination in the rotarod. We concluded that maternal (PhSe) 2 exposure during lactation increased selenium levels in the pup brain and caused changes on developmental and behavioral parameters of Wistar rat offspring. © 2006 Elsevier Inc. All rights reserved. Keywords: Selenium; Diphenyl diselenide; Developmental; Behavioral; Rat pups; Lactation 1. Introduction Rodents have a considerable postnatal development of the brain [12]. In fact, maturation lasts for several weeks of postnatal life, during which the brain is extremely sensitive to developmental disruption by chemical or environmental agents that can induce the appearance of adverse effects on postnatal development of the offspring. Since it is well established that fetal blood–brain barrier is not yet formed in pups at birth, drugs present in the milk would reach the offspring central nervous system (CNS), interfering with their development [1,3,28,29]. Selenium is recognized as an essential trace element and many of the lately found selenium-containing enzymes and proteins are obviously essential for normal growth, development and metabolism of an organism [5,11,14,33,34]. It becomes more and more apparent that the selenium plays a critical role in the maintenance of proper functioning of the nervous system. Selenium is a potent protective agent for neurons through the expression of selenoproteins, which are mostly involved in regulation of redox status under physiological conditions and in antioxidant defense [31]. However, despite the importance of selenium in brain physiology, it can also act as a significant environmental toxicant [9]. Diphenyl diselenide, (PhSe) 2 , is a common intermediate in organic reactions [22,40], that displays antioxidant actions, although it is also proposed to have neurotoxic properties. Extensive studies have focused on the potential toxicological and pharmacological effects of (PhSe) 2 in animal models (for review, see [25]). With regard to developmental effects, it has been recently reported that single and repeated (GD6 through 15) subcutaneous administration of (PhSe) 2 to pregnant rats during organogenesis induces only slight embryofetotoxicity [7,39]. There is some evidence that (PhSe) 2 crosses the blood–brain barrier and brain selenium levels increase in mice after acute and chronic exposure to (PhSe) 2 [21]. Furthermore, it has been established that organoselenium compounds affect a number of neuronal processes and the exposure to high doses of these compounds causes CNS effects in mice [15,25]. Recently, our group reported that simple organoselenium compounds, in- cluding (PhSe) 2 , present convulsant activity [24]. Likewise, it has been shown that (PhSe) 2 inhibits cerebral aminolevulinic Neurotoxicology and Teratology 28 (2006) 607 – 616 www.elsevier.com/locate/neutera ⁎ Corresponding author. Tel.: +55 55 3220 8140; fax: +55 55 3220 8978. E-mail address: criswn@quimica.ufsm.br (C.W. Nogueira). 0892-0362/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ntt.2006.08.003