Individual variation in cortisol responses to acute ‘on-back’ restraint in an outbred hamster François S. Guimont, Katherine E. Wynne-Edwards ⁎ Department of Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6 Received 7 November 2005; revised 3 March 2006; accepted 17 March 2006 Available online 12 May 2006 Abstract An outbred species of dwarf hamster (Phodopus campbelli) was used to assess between-individual variability in the response to, and recovery from, a one-time stressor of 6 min of physical restraint in a subordinate, on-back, position. Four repeated plasma samples were drawn under home- cage isoflurane anesthesia from 33 males and 38 females 50 min before, and then 10, 60, and 120 min after the stress onset. Plasma cortisol concentrations were higher in females than males, but there was no evidence for a sex difference in response to the stressor. The expected cross- sectional increase (∼ 50 ng/ml) in response to the stressor, followed by recovery, was seen. However, there was extensive individual variation, ranging from no reaction to continuous decline from the initial to the final sample. Results were expressed in four ways (absolute concentration, relative concentration, and area under the curve relative to ground and relative to the stress-induced increase) and also standardized and subjected to hierarchical cluster analysis. Clusters failed to effectively partition the between-individual variation and did not cluster by sex, age, or housing conditions. The current study cautions against ignoring individual differences and suggests that outbred animal models might be particularly relevant to understanding stress-related pathological conditions. © 2006 Elsevier Inc. All rights reserved. Keywords: Phodopus campbelli; Dwarf hamster; Cortisol; Cortisol amplitude; Stress; Stress reactivity; Individual differences Introduction One of the greatest challenges in understanding the complexities of the stress response is the difficulty encountered when trying to understand the extent of inter-individual variation (Moberg, 2000; Young et al., 2004; Hruschka et al., 2005). Glucocorticoids are responsive to stress and the majority of studies use the concentration of cortisol or corticosterone as a proxy for the magnitude of stress experienced by the individual (Erikson et al., 2003; Korte, 2001). However, the range of glucocorticoid concentrations in a cross-sectional analysis of any population can be large, and researchers have found advantages in experimental designs that use repeated measure- ments of glucocorticoid concentrations (Armario et al., 2004; Jones et al., 2000; Ramsay and Lewis, 2003). Such studies suggest that there is heterogeneity in the duration of time required for corticosteroid concentrations of mice (Veenema et al., 2003), rats (García and Armario, 2001; Meaney et al., 1993; Mormède et al., 2002), and humans (Mormède et al., 2002; Ramsay and Lewis, 2003; Richter et al., 1996) to return to their resting levels. Understanding the basis for the variation in corticosteroid dynamics may be important in explaining individual susceptibilities of the immune system (Barriga et al., 2002; Bilbo et al., 2003; Carlton et al., 2001; De Kloet et al., 1998; Korte, 2001), growth and development (Brown and Nestor, 1974; Castanon et al., 1994; Tsigos and Chrousos, 2002), and emotional states (Armario et al., 2004; Erikson et al., 2003; De Kloet, 2004; Roy et al., 2001; Young et al., 2004). The current study was designed to quantify and partition individual cortisol responses to a standardized stressor in an outbred population of rodents held under laboratory conditions. The model system chosen was the Djungarian dwarf hamster, Phodopus campbelli, because this population retains behavioral characteristics of the wild ancestral population from which it is derived, including entrainment of activity to the light-dark cycle Hormones and Behavior 50 (2006) 252 – 260 www.elsevier.com/locate/yhbeh ⁎ Corresponding author. Fax: +1 613 533 6617. E-mail address: wynneedw@biology.queensu.ca (K.E. Wynne-Edwards). 0018-506X/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.yhbeh.2006.03.008