Brain, Behavior, and Immunity 20 (2006) 488–497 www.elsevier.com/locate/ybrbi 0889-1591/$ - see front matter  2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbi.2005.10.004 Endocrine and immunological correlates of behaviorally identi Wed swim stress resilient and vulnerable rats Elizabeth A. Levay a , Antonina Govic a , Agnes Hazi a , Graham Flannery b , John Christianson c , Robert C. Drugan c , Stephen Kent a,¤ a School of Psychological Science, La Trobe University, Bundoora, Vic., Australia b Immunogenetics Laboratory, Department of Genetics, La Trobe University, Bundoora, Vic., Australia c Department of Psychology, University of New Hampshire, Durham, NH, USA Received 19 July 2005; received in revised form 4 October 2005; accepted 12 October 2005 Available online 23 November 2005 Abstract Animal models of stress-induced depression have identiWed a bimodal reactivity to stress, namely ‘resilience’ and ‘vulnerability.’ Possi- ble corresponding diVerences in endocrine and immunological responses between these groups have not been delineated. Male Sprague– Dawley rats were divided into three groups: stress (n D 25), conWned controls (n D 7), and home cage controls (n D 7). Stress rats were exposed to 80, 5-s inescapable cold water swim trials (15 °C). Twenty-four hours later, the stress rats were tested on an instrumental swim escape test (SET) but now they had access to an omnidirectional lever that terminated the stress. Immediately after the SET, trunk blood was collected to assay for serum corticosterone (CORT), and spleens were removed and natural killer cell activity (NKCA) and conca- navalin A (CON-A) induced lymphocyte proliferation determined. Subjects in the stress treatment group were divided into distinct ‘resil- ient’ and ‘vulnerable’ categories by a median split for average escape latencies across the last 25 trials of the SET. Stress rats secreted more CORT than controls and vulnerable rats secreted greater levels than resilient rats. NKCA was greatest in control rats, and was decreased in the stress rats although the resilient and the vulnerable groups did not diVer. Conversely, CON-A-induced lymphocyte proliferation was greatest in stress rats, vulnerable rats exhibiting more proliferation than resilient rats, but both were greater than both control groups. Stress animals were hypothermic throughout the swim stress procedures but exhibited a stress-induced fever following the initial swim tri- als. The observed diVerences may have important predictive and theoretical utility for vulnerable and resilient proWles.  2005 Elsevier Inc. All rights reserved. Keywords: Corticosterone; Natural killer cell activity; Lymphocyte proliferation; Psychoneuroimmunology; Body temperature 1. Introduction Stress has been proposed to play a role in the pathophys- iology of depressive illness (Wong and Licinio, 2001). As a result, a number of animal models have been developed to examine this relationship. In such models, exposure to ines- capable stress induces depressive symptoms that can be ameliorated with anti-depressant treatments (Porsolt et al., 1977; Sherman et al., 1982). The two most prominent animal models of depression are the inescapable shock (IS)-induced learned helplessness (LH) (Sherman et al., 1982) and the forced swim ‘behav- ioral despair’ model (Porsolt et al., 1977). Studies investi- gating the eVects of repeated IS in a variety of species have consistently reported the development of learning impair- ments when subjects are exposed to a subsequent session of shock in which escape is possible (Huang et al., 2004; Maier et al., 1973; Maier and Seligman, 1976; Petty et al., 1994; Seligman et al., 1975; Steciuk et al., 1999). These cognitive impairments are attributed to a form of learning termed ‘learned helplessness’ (LH), in which the animal learns in the initial shock session, having failed a number of attempts * Corresponding author. Fax: +61 39479 1956. E-mail address: S.Kent@latrobe.edu.au (S. Kent).