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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.5-羟色胺转运体基因敲除小鼠中5-羟色胺受体（5-HT1A）的密度和表达降低，但G蛋白偶联未受影响：性别和脑区差异
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J Pharmacol Exp Ther. 1999 Dec;291(3):999-1007.
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Decreased G-protein coupling of serotonin 5-HT(1A) receptors in the brain of 5-HT(1B) knockout mouse.5-羟色胺1B基因敲除小鼠大脑中5-羟色胺5-HT(1A)受体的G蛋白偶联减少。
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本文引用的文献

1
Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample.5-羟色胺转运体启动子多态性与以女性为主的人群样本中人格特质的关联。
Am J Med Genet. 2000 Apr 3;96(2):202-16. doi: 10.1002/(sici)1096-8628(20000403)96:2<202::aid-ajmg16>3.0.co;2-j.
2
Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivo.G蛋白在体内与下丘脑5-羟色胺1A受体偶联的证据。
J Neurosci. 2000 May 1;20(9):3095-103. doi: 10.1523/JNEUROSCI.20-09-03095.2000.
3
Recent progress in psychiatric genetics-some hope but no hype.精神病遗传学的最新进展——有希望但不炒作。
Hum Mol Genet. 2000 Apr 12;9(6):927-35. doi: 10.1093/hmg/9.6.927.
4
Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine.长期服用氟西汀的大鼠脑内5-羟色胺1A和5-羟色胺1B受体及5-羟色胺转运体的差异适应性
Neuropharmacology. 2000;39(1):110-22. doi: 10.1016/s0028-3908(99)00088-x.
5
A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo.一个与情感障碍相关的血清素转运体基因内含子2多态性区域，在小鼠胚胎中具有等位基因依赖性的差异增强子样特性。
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15251-5. doi: 10.1073/pnas.96.26.15251.
6
Effects of chronic 17beta-estradiol treatment on the serotonin 5-HT(1A) receptor mRNA and binding levels in the rat brain.慢性17β-雌二醇治疗对大鼠脑内5-羟色胺5-HT(1A)受体mRNA及结合水平的影响。
Synapse. 2000 Jan;35(1):39-44. doi: 10.1002/(SICI)1098-2396(200001)35:1<39::AID-SYN5>3.0.CO;2-T.
7
Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice.5-羟色胺（5-HT）(1A)介导的温度和神经内分泌反应以及5-HT转运体基因敲除小鼠中5-HT(1A)结合位点的减少
J Pharmacol Exp Ther. 1999 Dec;291(3):999-1007.
8
Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors.缺乏5-羟色胺1A或5-羟色胺1B受体的基因敲除小鼠的情绪状态改变。
Neuropsychopharmacology. 1999 Aug;21(2 Suppl):52S-60S. doi: 10.1016/S0893-133X(99)00047-0.
9
Reduced efficacy of 8-OH-DPAT's inhibition of lordosis behavior by prior estrogen treatment.预先进行雌激素处理会降低8-OH-DPAT对脊柱前凸行为的抑制效果。
Horm Behav. 1999 Jun;35(3):215-23. doi: 10.1006/hbeh.1999.1515.
10
Molecular manipulations as tools for enhancing our understanding of 5-HT neurotransmission.分子操作作为增进我们对5-羟色胺神经传递理解的工具。
Trends Pharmacol Sci. 1999 Jun;20(6):246-52. doi: 10.1016/s0165-6147(99)01325-5.

5-羟色胺转运体基因敲除小鼠中5-羟色胺受体（5-HT1A）的密度和表达降低，但G蛋白偶联未受影响：性别和脑区差异

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.

作者信息

Li Q, Wichems C, Heils A, Lesch K P, Murphy D L

机构信息

Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health Clinical Center, Bethesda, Maryland 20892-1264, USA.

出版信息

J Neurosci. 2000 Nov 1;20(21):7888-95. doi: 10.1523/JNEUROSCI.20-21-07888.2000.

DOI:10.1523/JNEUROSCI.20-21-07888.2000
PMID:11050108
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6772750/
Abstract

The aim of the present study was to investigate the mechanisms underlying the desensitization of 5-HT(1A) receptors in the dorsal raphe and hypothalamus of serotonin (5-HT) transporter knock-out mice (5-HTT -/-). The density of 5-HT(1A) 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-HT(1A) receptors also was decreased significantly in several nuclei of the hypothalamus, amygdala, and septum of female 5-HTT -/- mice. 5-HT(1A) 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-HT(1A) receptors and G-protein levels in most brain regions were not reduced significantly, except that G(o) and G(i1) proteins were reduced modestly in the midbrain of 5-HTT -/- mice. These data suggest that the desensitization of 5-HT(1A) receptors in 5-HTT -/- mice may be attributable to a reduction in the density of 5-HT(1A) receptors. This reduction is brain region-specific and more extensive in the female mice. The reduction in the density of 5-HT(1A) receptors may be mediated partly by reduction in the gene expression of 5-HT(1A) 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-HT(1A) receptors are unlikely to be involved in the desensitization of 5-HT(1A) receptors in 5-HTT -/- mice.

摘要

本研究的目的是探究血清素（5-HT）转运体基因敲除小鼠（5-HTT -/-）中缝背核和下丘脑5-HT(1A)受体脱敏的潜在机制。雄性和雌性5-HTT -/-小鼠中缝背核5-HT(1A)受体的密度均降低。这种降低在雌性5-HTT -/-小鼠中比在雄性5-HTT -/-小鼠中更显著。雌性5-HTT -/-小鼠不存在8-OH-DPAT诱导的体温过低现象，而在5-HTT +/-小鼠中则明显减弱。雌性5-HTT -/-小鼠下丘脑、杏仁核和隔区的几个核团中5-HT(1A)受体的密度也显著降低。雌性5-HTT +/-和5-HTT -/-小鼠中缝背核区域的5-HT(1A)受体mRNA显著减少，但下丘脑或海马体中未减少。除了5-HTT -/-小鼠中脑的G(o)和G(i1)蛋白略有减少外，大多数脑区中与5-HT(1A)受体偶联的G蛋白及G蛋白水平并未显著降低。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。这种降低具有脑区特异性，在雌性小鼠中更显著。5-HT(1A)受体密度的降低可能部分是由中缝背核中5-HT(1A)受体基因表达的减少介导的，但也可能是由5-HTT -/-雌性小鼠下丘脑的其他机制介导的。最后，与5-HT(1A)受体偶联的G蛋白的改变不太可能参与5-HTT -/-小鼠中5-HT(1A)受体的脱敏过程。