Tejani-Butt S M, Paré W P, Yang J
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104.
Brain Res. 1994 Jun 27;649(1-2):27-35. doi: 10.1016/0006-8993(94)91045-6.
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.
本研究比较了反复给予新异应激源对斯普拉格-道利（S-D）大鼠和威斯塔-京都（WKY）大鼠“抑郁行为”的影响，抑郁行为通过强迫游泳试验和旷场试验来定义。由于应激似乎会改变脑去甲肾上腺素（NE）活性，本研究还调查了应激源对S-D大鼠和WKY大鼠β-肾上腺素能受体（β-ARs）、α2-肾上腺素能受体（α2-ARs）和NE转运体（NET）位点的影响。与未应激的对照组相比，应激并未改变S-D大鼠中125I-碘吲哚洛尔（125I-PIN）与β-ARs的结合，也未改变[3H]咪唑克生（[3H]IDAZ）与α2-ARs的结合。然而，应激的WKY大鼠在皮质、海马、杏仁核和下丘脑显示出125I-IPIN与β-ARs的结合显著减少，在杏仁核中[3H]IDAZ与α2-ARs的结合减少。应激的WKY大鼠中[3H]尼索西汀（[3H]NIS）与NET位点的结合在皮质、海马和杏仁核中也减少。当比较两种品系时，最令人惊讶的发现是，与S-D大鼠相比，WKY大鼠海马和杏仁核中NET位点的密度显著更高。本研究结果表明，应激不仅会加剧WKY大鼠的抑郁行为，还会选择性地改变边缘脑区的β-ARs、α2-ARs和NET位点。因此，WKY品系可能是一种用于研究抑郁行为和新型抗抑郁药物的有用动物模型。
