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.
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104.
S M
SM
Tejani-Butt
W P
WP
Paré
J
J
Yang
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004146:Dioxanes / Q000378:metabolism; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D019329:Idazoxan; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013045:Species Specificity; D013315:Stress, Psychological / Q000378:metabolism*; D013550:Swimming; D027981:Symporters
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002352:Carrier Proteins; D004146:Dioxanes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011941:Receptors, Adrenergic; C493226:Slc6a2 protein, rat; D027981:Symporters; D005473:Fluoxetine; C011386:nisoxetine; C029247:3-iodopindolol; D010869:Pindolol; D009638:Norepinephrine; D019329:Idazoxan