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 blain 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 I-125-iodopindolol (I-125-PIN) binding to alpha-ARs, nor [H-3]idazoxan ([H-3]IDAZ) binding to alpha(2)-ARs in S-D rats, compared to non-stressed controls. However, WKY-stressed rats showed a significant reduction in I-125-IPIN binding to beta-ARs in the cortex, hippocampus, amygdala and hypothalamus, and a reduction in [H-3]IDAZ binding to alpha(2)-ARs in the amygdala. [H-3]nisoxetine ([H-3]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.