Changes of neuropeptide contents in rat brain after chronic interruption of dopaminergic transmission by administrations with haloperidol and 6-hydroxydopamine.

给予氟哌啶醇和 6-羟基多巴胺慢性阻断多巴胺能传递后大鼠脑中神经肽含量的变化。

• 批准号: 60570510
• 负责人: KATO Nobumasa
• 金额: $ 1.22万
• 依托单位: Shiga University of Medical Science (1986)国立武蔵療養所 (1985)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570510/
• 关键词: dopamine; cholecystokinin; somatostatin; haloperidol; 6-hydroxydopamine; prolactin; ラット

Effects of long-term treatment with haloperidol (HAL) were studied on brain immunoreactive cholecystokinin octapeptide (IR-CCK8) and on plasma prolactin (rPRL) in the rat. HAL treatment was conducted with continuous infusion via osmotic minipump implanted subcutaneously or with daily intraperitoneal injection (intermittent administration). Plasma rPRL levels remained elevated compared to those in controls following 14-days intermittent administration. In contrast, increased rPRL levels at the first day of continuous infusion with HAL disappeared quickly, to be replaced after 14-days by an inhibited release of rPRL. IR-CCK8 contents in the striatum and mesolimbic areas were increased following both continuous and intermittent administration with HAL. This change was more obvious 24 h after the final injection as compared to 1h after the injection. The results suggest that the tolerance can be developed in the tubero-infundibular dopamine system regulating rPRL-release, and that endogeno … More us CCK-8 may have a role in the chronic effect of HAL.Effects of intracerebroventricular administration with 6-hydroxydopamine (6-OH-DA) were investigated on IR-CCK8 and somatostatin(SRIF) in the rat brain. The animals were injected with whether 6-OH-DA alone or 6-OH-DA following the treatment with pargyline and desipramine and were killed by microwave irradiation 6 days after the treatment. The treatment with 6-OH-DA alone was found to deplete both DA and norepinephrine concentrations in all areas tested as documented previously. 6-OH-DA administration with or without pretreatment elevated the contents of IR-CCK8 and IR-SRIF in several regions including midbrain, striatum, frontal cortex and limbic forebrain, where DA neurones innervate. These results suggest that endogenous CCK-8 and SRIF are under the control of DA and that the populations of neurones which contain both DA and CCK8 are limited in relatively small areas of the rat brain and substantial CCK-8 innervations exist independently from DA neurones. Less

研究了氟哌啶醇（HAL）长期治疗对大鼠脑免疫反应性胆囊收缩素八肽（IR-CCK8）和血浆催乳素（rPRL）的影响。HAL治疗通过渗透微型泵皮下植入持续输注或每日腹腔内注射（间歇给药）进行。与对照组相比，在14天间歇给药后血浆rPRL水平仍然升高。相比之下，连续输注HAL第一天升高的rPRL水平迅速消失，14天后被rPRL的抑制释放所取代。连续和间歇给药HAL后，纹状体和中边缘区IR-CCK8含量均增加。这种变化在末次注射后24小时比注射后1小时更为明显。结果表明，调节rprl释放的结节-基底多巴胺系统可能产生耐受性，内源性的CCK-8可能在HAL的慢性效应中起作用。研究了6-羟基多巴胺（6-OH-DA）对大鼠脑IR-CCK8和生长抑素（SRIF）的影响。分别给小鼠单独注射6- oh - da，或在pargyline和地西帕明治疗后注射6- oh - da，并在治疗6天后用微波辐照处死。研究发现，单独使用6-OH-DA治疗后，所有测试区域的DA和去甲肾上腺素浓度均下降。6-OH-DA加预处理或不加预处理均可提高DA神经元活动的中脑、纹状体、额叶皮质和边缘前脑等区域IR-CCK8和IR-SRIF的含量。这些结果表明，内源性CCK-8和SRIF受DA控制，同时含有DA和CCK8的神经元群体局限于大鼠大脑的相对较小区域，大量CCK-8神经支配独立于DA神经元存在。少

项目成果

加藤進昌,ほか: 精神薬療基金研究年報. 17. 82-88 (1986)

Nobumasa Kato 等人：精神药物治疗基金研究年度报告 17. 82-88 (1986)。

Teruhiko Higuchi et al.: European Jearnal of Pharmacology. 125. 169-175 (1986)

Teruhiko Higuchi 等人：《欧洲药理学杂志》。

Kato N, Higuchi T, Igarashi Y and Moroji T: "Increase in immunoreactive cholecystokinin-octapeptide (IR-CCK8) contents in rat brain after chronic interruption of dopaminergic transmission produced by the administrations with haloperidol and 6-hydroxydopam

Kato N、Higuchi T、Igarashi Y 和 Moroji T：“服用氟哌啶醇和 6-羟基多巴造成的多巴胺能传递慢性中断后，大鼠脑中免疫反应性胆囊收缩素八肽 (IR-CCK8) 含量增加

Nobumasa Kato et al.: Society for Neuroscience Abstracts. 12. 232 (1986)

加藤信正 (Nobumasa Kato) 等人：神经科学学会文摘。

加藤進昌,兜真徳 共著: "神経ペプチドの基礎と臨床-精神疾患へのアプローチ-" 金剛出版(東京), 212 (1987)

加藤 Shinsho 和 Kabuto Masanori 合着：“神经肽的基础和临床应用 - 精神障碍的治疗方法”Kongo Publishing（东京），212（1987）