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大鼠下丘脑的神经降压素灌注:多巴胺释放与体温变化的分离

Neurotensin perfusion of rat hypothalamus: dissociation of dopamine release from body temperature change.

作者信息

Myers R D, Lee T F

出版信息

Neuroscience. 1984 May;12(1):241-53. doi: 10.1016/0306-4522(84)90150-7.

DOI:10.1016/0306-4522(84)90150-7
PMID:6462447
Abstract

To determine whether endogenous dopamine is involved in the impairment of body temperature induced by neurotensin, the local activity of [14C]dopamine in the hypothalamus of the unanesthetized rat was examined. A push-pull guide tube was implanted permanently above an intended site of perfusion within the anterior hypothalamic, pre-optic area or other region of the diencephalon. After the endogenous stores of dopamine at a specific site were labelled by microinjection of 0.02-0.05 muCi of [14C]dopamine, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 microliter/min and at successive 5 min intervals. Perfusion of neurotensin in concentrations of 0.05 or 0.1 microgram/microliter in the dorsomedial hypothalamus, lateral hypothalamus, arcuate nucleus or diagonal band of Broca evoked a calcium-dependent efflux of [14C]dopamine. The release of dopamine induced by neurotensin was functionally specific since it was: (1) not mimicked by the relatively inactive neurotensin analogue, [D-Arg9]neurotensin; (2) dependent on the morphological locus of the push-pull perfusion; and (3) not accompanied by an efflux of [3H]norepinephrine when the site was double-labelled. Although neurotensin perfused in the anterior hypothalamic, pre-optic area caused a consistent decline in temperature, in most cases the temperature change did not correlate with an enhanced release of dopamine. Moreover, the release of dopamine, but not the temperature change, was abolished when neurotensin was perfused in a calcium-free medium. These results show that it is unlikely that the thermolytic action of neurotensin, at least within the hypothalamus, is mediated by the presynaptic release of dopamine.

摘要

为了确定内源性多巴胺是否参与神经降压素引起的体温损害,研究了未麻醉大鼠下丘脑内[14C]多巴胺的局部活性。将推挽式导管永久性植入下丘脑前部、视前区或间脑其他区域内预期的灌注部位上方。在通过微量注射0.02 - 0.05微居里的[14C]多巴胺标记特定部位的内源性多巴胺储备后,以20微升/分钟的速度在该部位灌注人工脑脊液,每隔5分钟连续灌注。在下丘脑背内侧、下丘脑外侧、弓状核或布罗卡斜带中灌注浓度为0.05或0.1微克/微升的神经降压素,可诱发[14C]多巴胺的钙依赖性流出。神经降压素诱导的多巴胺释放具有功能特异性,因为:(1) 相对无活性的神经降压素类似物[D - Arg9]神经降压素不能模拟该作用;(2) 取决于推挽式灌注的形态学部位;(3) 当该部位进行双重标记时,不伴有[3H]去甲肾上腺素的流出。尽管在前下丘脑、视前区灌注神经降压素会导致体温持续下降,但在大多数情况下,体温变化与多巴胺释放增加无关。此外,当在无钙培养基中灌注神经降压素时,多巴胺的释放被消除,但体温变化未被消除。这些结果表明,神经降压素的解热作用,至少在下丘脑内,不太可能由多巴胺的突触前释放介导。

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