A study of the histamine neuron system : Its correlation to newly-discovered hypothalamic peptides.

食欲素是一种仅位于下丘脑外侧区神经元中的神经肽，它向大多数单胺能核发送投射，如去肾上腺素能蓝斑核、多巴胺能腹侧被皮层核和组胺能结节乳头核。本研究旨在研究食欲素在小鼠伤害感觉中的作用。通过对C57BL/6小鼠脑室内、鞘内和皮下注射食欲素A和B，揭示了这些肽的作用位点，并通过四种伤害性任务检测了疼痛阈值。在所有四种类型的热（热板，甩尾，脱爪），机械（尾压），化学（福尔马林，辣椒素和腹部拉伸）伤害和伤害肽诱导的行为反应试验中，当给药时，食欲素显示出抗伤害性作用，而s.c.给药无效。食欲素A的抗感觉作用比食欲素b的更明显、更持久。食欲素A的体外给药与体外给药一样有效，甚至比体外给药更有效。1型腺苷受体拮抗剂1,3-二丙基-8-环戊基黄嘌呤（DPCPX）和茶碱能完全阻断食欲素的作用，但纳洛酮不能，这表明可能涉及含腺苷的神经元和/或腺苷途径参与这些食欲素的作用。痛觉肽灌胃对脑和脊髓中食欲素的表达无显著影响。目前的研究结果表明，食欲素在至少四种不同类型的疼痛中具有抗痛觉作用，可能同时作用于大脑和脊髓。越来越多的证据表明，组胺能神经元系统与精神分裂症的病理生理有关。本研究采用正电子发射断层扫描（PET）技术比较精神分裂症患者与正常人体内组胺H_1受体的分布。采用PET和H_1受体放射配体[^<11>C]多塞平检测10例正常人和10例服药精神分裂症患者的H_1受体结合情况。采用逐体素的图形分析方法计算[^<11 bb0 C]多肽对脑内可用H_1受体的结合电位（BP=Bmax/K_D），并利用感兴趣区域（roi）和统计参数映射（SPM99）对精神分裂症和正常受试者进行比较。精神分裂症患者脑额叶、前额叶皮层和扣带回H_1受体的BP值明显低于对照组。相反，精神分裂症患者的H_1受体并没有明显高于对照组。我们的研究结果表明，中枢组胺能神经元系统可能参与精神分裂症的病理生理，尽管需要进一步的研究来证实这一假设。少

Orexins are neuropeptides located exclusively in neurons of the lateral hypothalamic area, which send projections to most monoaminergic nuclei, such as noradrenergic locus coeruleus, dopaminergic ventral tegmental areas, and histaminergic tuberomammillary nuclei. The present work was carried out to examine the role of orexins in nociception in mice. C57BL/6 mice were administered with orexin A and B intracerebroventricularly(i.c.v.), intrathecally(i.t.) and subcutaneously(s.c.) to reveal the sites of action of these peptides and to examine the pain thresholds using four kinds of nociceptive tasks. Orexins showed antinociceptive effects in all four types of assays for thermal (hot-plate, tail-flick, paw-withdrawal), mechanical (tail-pressure), chemical (formalin, capsaicin and abdominal stretch) nociceptions and nociceptininduced behavioral responses, when administered i.c.v. or i.t., whereas the s.c. administration was ineffective. The antinociceptive effects of orexin A were more rema … More rkable than those of orexin B. The i.c.v. administration of orexin A was as effective as, or more potent than the i.t. administration. The effects of orexinAwere completely blocked by adenosine type 1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and theophylline, but not by naloxone, suggesting a possible involvement of the adenosine-containing neurons and/or the adenosine pathway in these orexin actions. The i.c.v. administration of nociceptin had no significant effects on orexin expression in the brain and spinal cord. The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord.Increasing evidence has shown that the histaminergic neuron system is implicated in the pathophysiology of schizophrenia. The aim of this study was to compare the distribution of histamine H_1 receptors between schizophrenics and normal human subjects in vivo using positron emission tomography (PET). H_1 receptor binding was measured in 10 normal subjects and 10 medicated schizophrenic patients by PET and [^<11>C] doxepin, a radioligand for the H_1 receptor. The binding potential (BP=Bmax/K_D) of [^<11>C] doxepin for available brain H_1 receptors was calculated by a graphical analysis on voxel-by-voxel basis and compared between schizophrenics and normal subjects using the regions of interest (ROIs) and the statistical parametrical mapping (SPM99). BP values for H_1 receptors in the frontal and prefrontal cortices and the cingulate gyrus were significantly lower among the schizophrenic patients than among the control subjects. On the contrary, there were no areas of the brain where H_1 receptors were significantly higher among the schizophrenic patients than the control subjects. The results of our study suggest that the central histaminergic neuron system could be involved in the pathophysiology of schizophrenia, although further studies are needed to confirm this hypothesis. Less