Physical defeat reduces the sensitivity of murine splenocytes to the suppressive effects of corticosterone

Social disruption (SDR) in male mice reduces the sensitivity of their splenocytes to the actions of glucocorticoids. To determine whether physical defeat is necessary for the development of this reduced sensitivity, a modification of the SDR paradigm was employed in which mice were exposed to fighting conspecifics in the presence or absence of physical contact. This was accomplished by dividing a cage of 5 resident male C57BL/6 mice in half with a wire mesh partition so that 2 of the mice in the cage (SDR Physical Contact mice) fought and were defeated by an aggressive male C57BL/6 intruder that was placed into the cage for 2 h for up to 6 days, while the remaining 3 resident mice (SDR Sensory Contact mice) were on the opposite side of the partition and thus prevented from physically interacting with the intruder. Although both the SDR Physical Contact and the SDR Sensory Contact mice had significantly elevated corticosterone levels and displayed submissive postures toward the intruder, only the SDR Physical Contact animals developed functional glucocorticoid resistance. The viability of LPS-stimulated splenocytes cultured from the SDR Physical Contact mice was not affected by pharmacological doses of corticosterone, whereas splenocyte viability was significantly reduced by corticosterone in cultured cells from SDR Sensory Contact and control mice. This study indicates that exposure to a stressful environment in the absence of physical attack does not reduce the sensitivity of murine splenocytes to the suppressive effects of corticosterone. (C) 2004 Elsevier Inc. All rights reserved.