Reduction in the Density and Expression, But Not G-Protein Coupling, of Serotonin Receptors (5-HT1A) in 5-HT Transporter Knock-Out Mice: Gender and Brain Region Differences
Reduction in the Density and Expression, But Not G-Protein Coupling, of Serotonin Receptors (5-HT1A) in 5-HT Transporter Knock-Out Mice: Gender and Brain Region Differences
复制标题
5-HT 转运蛋白敲除小鼠中血清素受体 (5-HT1A) 的密度和表达减少，但 G 蛋白偶联未减少：性别和脑区差异
作者：
Qian Li;Christine Wichems;A. Heils;K. Lesch;D. Murphy
本研究旨在探讨5-HT转运体基因敲除小鼠中缝背核和下丘脑5-HT 1A受体脱敏的机制。雄性和雌性5-HTT −/−小鼠中缝背核中5-HT 1A受体的密度均降低。雌性5-HTT −/−小鼠的这种减少比雄性小鼠更广泛。8-OH-DPAT诱导的体温降低在雌性5-HTT −/−小鼠中不存在，在5-HTT +/−小鼠中明显减弱。雌性5-HTT −/−小鼠的下丘脑、杏仁核和隔核的几个核团中5-HT 1A受体的密度也显著降低。在雌性5-HTT +/−和5-HTT −/−小鼠的中缝背核区域，5-HT 1A受体mRNA显著减少，但在下丘脑或海马中没有。与5-HT 1A受体偶联的G蛋白和大多数脑区的G蛋白水平没有显著降低，除了Go和Gi 1蛋白在5-HTT −/−小鼠的中脑中适度降低。这些数据表明，5-HTT −/−小鼠中5-HT 1A受体的脱敏可能归因于5-HT 1A受体密度的降低。这种减少是大脑区域特异性的，在雌性小鼠中更广泛。5-HT 1A受体密度的降低可能部分由中缝背核中5-HT 1A受体基因表达的降低介导，但也可能由5-HTT −/−雌性小鼠下丘脑中的其他机制介导。最后，G蛋白与5-HT 1A受体偶联的改变不太可能参与5-HTT −/−小鼠中5-HT 1A受体的脱敏。
The aim of the present study was to investigate the mechanisms underlying the desensitization of 5-HT1A receptors in the dorsal raphe and hypothalamus of serotonin (5-HT) transporter knock-out mice (5-HTT −/−). The density of 5-HT1A receptors in the dorsal raphe was reduced in both male and female 5-HTT −/− mice. This reduction was more extensive in female than in male 5-HTT −/− mice. 8-OH-DPAT-induced hypothermia was absent in female 5-HTT −/− and markedly attenuated in 5-HTT +/− mice. The density of 5-HT1A receptors also was decreased significantly in several nuclei of the hypothalamus, amygdala, and septum of female 5-HTT −/− mice. 5-HT1A receptor mRNA was reduced significantly in the dorsal raphe region, but not in the hypothalamus or hippocampus, of female 5-HTT +/− and 5-HTT −/− mice. G-protein coupling to 5-HT1A receptors and G-protein levels in most brain regions were not reduced significantly, except that Go and Gi1 proteins were reduced modestly in the midbrain of 5-HTT −/− mice. These data suggest that the desensitization of 5-HT1A receptors in 5-HTT −/− mice may be attributable to a reduction in the density of 5-HT1A receptors. This reduction is brain region-specific and more extensive in the female mice. The reduction in the density of 5-HT1A receptors may be mediated partly by reduction in the gene expression of 5-HT1A receptors in the dorsal raphe, but also by other mechanisms in the hypothalamus of 5-HTT −/− female mice. Finally, alterations in G-protein coupling to 5-HT1Areceptors are unlikely to be involved in the desensitization of 5-HT1A receptors in 5-HTT −/− mice.
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DOI：
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