Effect of repeated novel stressors on depressive behavior and brain norepinephrine receptor system in Sprague-Dawley and Wistar Kyoto (WKY) rats.

This study compared the effects of repeated novel stressors on 'depressive behaviors', defined by the forced-swim and open-field tests, in Sprague-Dawley (S-D) and Wistar Kyoto (WKY) rats. Since stress appears to alter brain norepinephrine (NE) activity, this study also investigated the effects of the stressors on beta-adrenoceptors (beta-ARs), alpha 2-adrenoceptors (alpha 2-ARs) and NE transporter (NET) sites in S-D and WKY rats. Stress did not alter 125I-iodopindolol (125I-PIN) binding to beta-ARs, nor [3H]idazoxan ([3H]IDAZ) binding to alpha 2-ARs in S-D rats, compared to non-stressed controls. However, WKY-stressed rats showed a significant reduction in 125I-IPIN binding to beta-ARs in the cortex, hippocampus, amygdala and hypothalamus, and a reduction in [3H]IDAZ binding to alpha 2-ARs in the amygdala. [3H]nisoxetine ([3H]NIS) binding to NET sites in WKY-stressed rats was also reduced in the cortex, hippocampus and amygdala. When both strains were compared, the most surprising finding was a significantly higher density of NET sites in the hippocampus and amygdala in WKY rats compared to S-D rats. The results of this study indicate that stress, not only exacerbates depressive behavior in WKY rats, but also selectively alters beta-ARs, alpha 2-ARs and NET sites in limbic brain regions. Thus, the WKY strain may serve as a useful animal model for depressive behavior and for the investigation of novel antidepressant drugs.