Psychological stressors as a model of maternal adversity: Diurnal modulation of corticosterone responses and changes in maternal behavior Marion Léonhardt a , Stephen G. Matthews b , Michael J. Meaney a , Claire-Dominique Walker a, a CIHR program in Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Quebec, Canada H4H 1R3 b Department of Physiology, Medicine and Obstetrics and Gynaecology, University of Toronto, Toronto, Canada M5S 1A8 Received 24 May 2006; revised 23 August 2006; accepted 28 August 2006 Available online 10 October 2006 Abstract Maternal adversity is associated with long-lasting consequences on cognitive development, behavior and physiological responses in rat offspring. Few studies have examined whether repeated maternal stress produces repeated activation of the hypothalamuspituitaryadrenal (HPA) axis in mothers and whether it modifies maternal behavior. Here, we tested a novel model of perinatal stress using repeated exposure to purelypsychological stressors throughout the gestation and lactation periods in rats. We first tested the diurnal influences of repeated 1-h strobe light exposure on maternal corticosterone secretion. Despite the hyporesponsiveness to stress documented in late pregnant and lactating mothers, we observed an enhanced response to strobe light in the afternoon compared to the morning in stressed mothers during lactation. Next, dams were exposed to 24-h forced foraging followed by 10-h wet bedding during the diurnal peak of corticosterone secretion. Although no corticosterone responses to forced foraging and wet bedding were observed, the combination of both stressors had a significant effect on maternal behavior. Motherpup interactions were significantly altered during the first 8 days of lactation. Taken together, these findings suggest that lactating mothers maintain responsiveness to specific and repeated psychological stressors, in particular at the time of the diurnal peak in corticosterone secretion. Depending on the stressor applied, either neuroendocrine activation or changes in maternal behavior might be important determinants of the long- term consequences in the offspring. The combination of forced foraging, wet bedding and strobe light might represent a novel model of mild maternal adversity using purelypsychological stressors. © 2006 Elsevier Inc. All rights reserved. Keywords: Maternal stress; Corticosterone; Maternal behavior; Diurnal stress response; Forced foraging; Wet bedding Introduction Human epidemiological data as well as animal studies consistently show that early life stress is associated with defects in cognitive and affective development as well as impaired physiological stress responses (Meaney and Szyf, 2005; Pryce et al., 2005; Mirescu et al., 2004; Chapillon et al., 2002; Lemaire et al., 2000; Vallee et al., 1999; Cianfarani et al., 1998; Maccari et al., 1995), which increases the susceptibility to physiological and psychological pathologies later in life (for reviews see Seckl, 2001; Weinstock, 2001; Matthews, 2002). Such programming is thought to be a consequence of complex interactions between differential gene expression or vulnerabil- ity factors, stress hormones released by the hypothalamic pituitaryadrenal (HPA) axis in mothers (Kapoor et al., 2006), and variations in maternal care (for reviews see Fish et al., 2004; De Kloet et al., 2005). In rats, the perinatal period represents a critical window for brain development (Avishai-Eliner et al., 2002; Morgane et al., 1993). A burst of brain growth and a rapid neuroendocrine maturation occur during this period which makes the brain highly vulnerable to environmental program- ming (Meaney and Szyf, 2005; Ozanne and Hales, 2002; Matthews, 2002). Several paradigms of prenatal and perinatal maternal stress have been used to induce behavioral and biological dysfunctions in rodent offspring, including immobi- lization or restraint in a plastic cylinder (Maccari et al., 1995; Rojo et al., 1985; Smith et al., 2004), novel environment exposure (Muir et al., 1985; Maestripieri et al., 1991), immersion Hormones and Behavior 51 (2007) 77 88 www.elsevier.com/locate/yhbeh Corresponding author. Douglas Hospital Research Center, 6875 Lasalle Blvd, Verdun, QC, Canada H4H 1R3. Fax: +1 514 762 3034. E-mail address: waldom@douglas.mcgill.ca (C.-D. Walker). 0018-506X/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yhbeh.2006.08.008