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

Abstract

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), α 2-adrenoceptors ( α 2-ARs ) and NE transporter (NET) sites in S-D and WKY rats. Stress did not alter 125I-iodopindolol ( 125I-PIN) binding to β-ARs, nor [ 3H]idazoxan ([ 3H]IDAZ) binding to α 2-ARs in S-D rats, compared to non-stressed controls. However, WKY-stressed rats showed a significant reduction in 125I-IPIN binding to β-ARs in the cortex, hippocampus, amygdala and hypothalamus, and a reduction in [ 3H]IDAZ binding to α 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 β-ARs, α 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.