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 β-adrenoceptors (β-ARs),α₂-adrenoceptors (α₂-ARs) and NE transporter (NET) sites in S-D and WKY rats. Stress did not alter¹²⁵I-iodopindolol (¹²⁵I-PIN) binding to β-ARs, nor [³H]idazoxan ([³H]IDAZ) binding toα₂-ARs in S-D rats, compared to non-stressed controls. However, WKY-stressed rats showed a significant reduction in¹²⁵I-IPIN binding to β-ARs in the cortex, hippocampus, amygdala and hypothalamus, and a reduction in [³H]IDAZ binding toα₂-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 β-ARs,α₂-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.