Amplified behavioral and endocrine responses to forced swim stress in the Wistar-Kyoto rat.

The Wistar Kyoto (WKY) rat may be a useful model for the study of depressive behavior because they exhibit exaggerated responses to a number of stressors. These studies compared the behavioral and endocrine responses to swimming stress in WKY rats with Sprague-Dawley (SD) rats. In the first experiment, the onset of behavioral immobility and the endocrine stress responses (adrenocorticotropin hormone (ACTH) and corticosterone (CORT)) were examined as the duration of a swimming session was increased. In the second experiment, WKY and SD rats were swum for 15 min, then sacrificed at different intervals after completion of the swim, to examine the time course of endocrine stress responses. The final experiment compared the suppression of ACTH and CORT secretion by dexamethasone of peak diurnal ACTH and CORT levels in WKY and SD rats. Behaviorally, the WKY rats displayed early and prolonged immobility compared to SD rats regardless of the length of the swim stress. Plasma CORT and ACTH increased in WKY and SD rats as the duration of the stressor lengthened. The swim stress (15 min) produced higher levels of ACTH and CORT secretion at the end of the stress interval that persisted after termination of the stressor in WKY compared to SD rats. Peak diurnal CORT levels, but not ACTH levels, were higher in WKY than in SD rats. Dexamethasone suppressed ACTH levels less in WKY than in SD rats. These results indicate that the WKY rat that displays increased behavioral immobility also demonstrates exaggerated secretion of stress hormones during swimming stress, and the results may be due, in part, to reduced sensitivity of glucocorticoid receptors that supply negative feedback to the hypothalamic-pituitary-adrenal axis. The exaggerated behavioral and endocrine stress responses in the WKY rat support its potential usefulness as a model for studying stress-evoked depressive behavior.