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Is the hypothalamic paraventricular nucleus-locus coeruleus neuronal circuit involved in persistent increase in the plasma cortisol?

下丘脑室旁核-蓝斑神经元回路是否参与血浆皮质醇的持续增加？

基本信息

批准号：
17591217
负责人：
OKADA Shoshiro
金额：
$ 2.37万
依托单位：
Kochi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

The present study was undertaken to clarify the central mechanisms, involved in the intracerebroventricularly administered corticotropin-releasing factor-induced elevation of plasma corticosterone in urethane- and α-chloralose-anesthetized rats using microdialysis and immunohistochemical techniques. When corticotropin-releasing factor was given at 0.5,1.5,and 3.0 nmol/animal intracerebroventricularly, it dose-dependently increased noradrenaline release but not adrenaline release in the hypothalamic paraventricular nucleus. The 1.5 nmol/animal dose of corticotropin-releasing factor-induced noradrenaline release was attenuated by CP-154,526 (butyl-ethyl-{2,5-dimethy1-7-(2,4,6trimethylpheny1)-7H-pyrrolo [2,3-d] pyrimidin-4-yl} amine), a selective corticotropin-releasing factor 1 receptor antagonist, at 1.3 mol/animal, intracerebroventricularly, and was also abolished by phentolamine at 0.66 mol/animal, intracerebroventricularly. In addition, the corticotropin-releasing factor-induced elev … More ation of noradrenaline release in-the hypothalamic paraventricular nucleus and plasma corticosterone were abolished by hexamethonium, a nonselective nicotinic acetylcholine receptor antagonist, at 1.8 μmol/animal, intracerebroventricularly, and α-conotoxin MII, a potent α_3β_2 nicotinic acetylcholine receptor antagonist, at 30 nmol/animal, i.c.v. Corticotropin-releasing factor at 1.5 nmol/animal, i.c.v. evoked a significant expression of cFos, an immediate-early gene product, on the dopamine-β-hydroxylase-containing neurons and α_3 nicotinic acetylcholine receptor subunit-expressing neurons in the locus coeruleus, but not in the medullary A_1 and A_2 regions containing noradrenergic neurons. These results suggest that centrally administered corticotrophin-releasing factor elevates plasma corticosterone by the corticotropin-releasing factor 1 receptor and α_3 subunit-containing nicotinic acetylcholine receptor (probably α_3 β_2 nicotinic acetylcholine receptor) mediated activation of the locus coeruleus noradrenergic neurons projecting to the paraventricular nucleus in rats Less

本研究采用微透析和免疫组织化学技术，探讨了侧脑室注射促肾上腺皮质激素释放因子引起乌拉坦和α氯醛糖麻醉大鼠血浆皮质酮升高的中枢机制。侧脑室注射促肾上腺皮质激素释放因子0.5、1.5和3.0nmol/只，可剂量依赖性地增加下丘脑室旁核去甲肾上腺素的释放，但不增加肾上腺素的释放。侧脑室注射选择性促肾上腺皮质激素释放因子1受体拮抗剂CP-154,526(butyl-ethyl-{2，5-dimethy1-7-(2，4，6trimethylpheny1)-7H-pyrrolo[2，3-d]嘧啶-4-基}胺(CP-154,526[2，3-d]嘧啶-4-基}胺)可减弱促肾上腺皮质激素释放因子的1.5nmo1/动物剂量，脑室注射酚妥拉明(0.66mol/只)可阻断1.5nmol/动物剂量的促肾上腺皮质激素释放。此外，促肾上腺皮质激素释放因子诱导的ELEV…下丘脑室旁核去甲肾上腺素和血浆皮质酮的增加可被脑室注射非选择性烟碱型乙酰胆碱受体拮抗剂六甲溴铵和30nμ/只烟碱型乙酰胆碱受体拮抗剂α芋螺毒素MII和α_3β_2烟碱型乙酰胆碱受体拮抗剂阻断。促肾上腺皮质激素释放因子为1.5nmol/只，i.c.v。即刻早期基因产物CFos在蓝斑多巴胺β羟基酶阳性神经元和α_3烟碱型乙酰胆碱受体亚单位阳性神经元上有显著表达，但在延髓A1和A2区去甲肾上腺素能神经元上无明显表达。这些结果表明，中枢应用促肾上腺皮质激素释放因子可通过促肾上腺皮质激素释放因子1受体和含有α_3亚单位的烟碱型乙酰胆碱受体(可能是α_3、β_2烟碱型乙酰胆碱受体)激活大鼠蓝斑去甲肾上腺素能投射到室旁核的神经元，从而提高血浆皮质酮水平。