The effects of chronic mild stress on male Sprague-Dawley and Long Evans rats: I. Biochemical and physiological analyses

Document Type



Brain and Mind Institute


The chronic unpredictable mild stress (CMS) is a paradigm developed in animals to model the relatively minor and unanticipated irritants that lead to a state of anhedonia in some individuals. However, the effectiveness of CMS is sometimes difficult to establish, for which unique strain sensitivities has been attributed as one contributing factor. These considerations led us to design the present study, which was an investigation of the corticosterone response to CMS in two outbred rat strains--Sprague-Dawley and Long Evans. Animals were exposed to one of two conditions--control or CMS--for 3 weeks during which body weight and fecal count were regularly monitored. At the end of this period, blood was sampled at a variety of time intervals following induction of a brief restraint stressor. First, a significant effect of CMS on corticosterone levels was evident at time 0 (prior to the application of the acute restraint stressor) in both strains. Second, the typical quadratic pattern of stressor-elicited fluctuations in this measure was similar in both Sprague-Dawley and Long Evans rats, with consistently elevated levels for the first hour following exposure to the acute stressor; near baseline values were observed at 2 h. However, only in the Long Evans strain were CMS related values much less than that observed in the control group after restraint stress. Third, both strains showed a reduced weight gain in the CMS groups relative to control groups. Fourth, spleen and adrenal weights were similar across all groups. Fifth, fecal counts remained stable across weeks of treatment in all groups with the exception of the Long Evans rats exposed to CMS; in this group, average counts were systematically reduced over the treatment period. We conclude that a history of chronic stress significantly blunts corticosterone levels in Long Evans but not Sprague-Dawley rats following exposure to an acute stressor. Physiological indices however are less influenced by this experience, at least when the exposure is limited to 3 weeks.


This work was published before the author joined Aga Khan University.


Behavioural Brain Research