Jiao Xilu, Paré William P, Tejani-Butt Shanaz
Department of Pharmacology and Toxicology, University of the Sciences in Philadelphia, Box 118, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):913-9. doi: 10.1016/S0278-5846(03)00150-7.
The Wistar Kyoto (WKY) rat has long been proposed as an animal model of depressive behavior. Exposure to stress produces symptoms such as anhedonia, psychomotor retardation, ambivalence, and negative memory bias. Autoradiographic studies have revealed significant differences in the density of norepinephrine transporter (NET) and serotonin transporter (5-HTT) sites in several brain regions in WKY rats compared to Sprague-Dawley (S-D) rats. Since the mesolimbic dopamine (DA) system is involved in cognitive, emotional, and motivational behaviors, this study examined the distribution of dopamine transporter (DAT) sites in the brains of WKY compared to Wistar (WIS) and S-D rats. DAT sites were labeled with [3H]-GBR12935 (1 nM), and mazindol (50 microM) was used to define nonspecific binding. Quantitative analysis of the specific binding indicated that WKY rats exhibited significant differences in DAT binding sites in the cell body as well as mesolimbic areas in comparison to WIS and S-D rats. While the binding of [3H]-GBR to DAT sites was significantly decreased in the nucleus accumbens (NAc), the amygdala, the ventral tegmental area (VTA), and the reticular part of the substantia nigra (P<.05), the binding was significantly increased in the hippocampal subregions and the hypothalamus (P<.05) in WKY rats compared to the other two strains. In contrast, no strain differences were found in the caudate-putamen. The observed differences in the density and distribution of DAT sites in WKY rats may lead to altered modulation of synaptic DA levels in the cell body and mesolimbic regions, thereby contributing to the noted depression-like behaviors reported in this rat strain.
长期以来，Wistar Kyoto（WKY）大鼠一直被用作抑郁行为的动物模型。暴露于应激会产生诸如快感缺失、精神运动迟缓、矛盾情绪和负性记忆偏差等症状。放射自显影研究表明，与Sprague-Dawley（S-D）大鼠相比，WKY大鼠多个脑区去甲肾上腺素转运体（NET）和5-羟色胺转运体（5-HTT）位点的密度存在显著差异。由于中脑边缘多巴胺（DA）系统参与认知、情感和动机行为，本研究检测了WKY大鼠与Wistar（WIS）大鼠和S-D大鼠相比，其大脑中多巴胺转运体（DAT）位点的分布情况。用[3H]-GBR12935（1 nM）标记DAT位点，并用吗茚酮（50 microM）确定非特异性结合。特异性结合的定量分析表明，与WIS大鼠和S-D大鼠相比，WKY大鼠在细胞体以及中脑边缘区域的DAT结合位点存在显著差异。与其他两个品系相比，WKY大鼠伏隔核（NAc）、杏仁核、腹侧被盖区（VTA）和黑质网状部中[3H]-GBR与DAT位点的结合显著降低（P<0.05），而海马亚区和下丘脑的结合显著增加（P<0.05）。相比之下，尾状核-壳核未发现品系差异。WKY大鼠中观察到的DAT位点密度和分布差异可能导致细胞体和中脑边缘区域突触DA水平的调节改变,从而导致该大鼠品系出现明显的抑郁样行为。
