The mesolimbic system, denervation and the climbing response in the mouse.
The mesolimbic system, denervation and the climbing response in the mouse.
复制标题
小鼠的中脑边缘系统、去神经支配和攀爬反应。
DOI：
10.1016/0014-2999(80)90144-2
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发表时间：
1980
影响因子：
5
通讯作者：
V. Nohria
中科院分区：
文献类型：
--
作者：
B. Costall;D. Fortune;R. Naylor;V. Nohria
双侧伏隔内 6-OHDA（在 DMI 和反苯环丙明存在下为 2 μg，术后第 14 天）增强了小鼠对阿朴吗啡和 2-(N,N-二丙基)氨基-5,6-二羟基四氢化萘的攀爬反应，导致正常对数剂量反应曲线向左平行移动。阿扑吗啡反应的增强取决于 6-OHDA 的剂量，阈值 0.5 μg，最大剂量 2 μg。术后第 5 天，攀爬能力明显增加，第 10 天达到最大，然后在整个实验期间（6-8 周）保持不变。 0.25-2 μg 伏隔内 6-OHDA 引起中脑边缘区域（伏核和嗅结节）多巴胺含量的剂量相关降低，但不引起中脑边缘去甲肾上腺素或纹状体多巴胺的显着变化。在没有 DMI/反苯环丙胺的情况下，2 和 4 μg 6-OHDA 也会降低中脑边缘去甲肾上腺素和纹状体多巴胺含量。向纹状体注射 16 μg 6-OHDA（DMI/反苯环丙明后）使纹状体多巴胺含量降低 85%（不改变中脑边缘多巴胺或去甲肾上腺素含量），但这种治疗未能改变阿朴吗啡攀爬（术后第 2-12 天）。氟哌啶醇、舒必利、硫利达嗪、氯氮平和甲氧氯普胺均导致正常小鼠和 6-OHDA 治疗小鼠的阿朴吗啡攀爬量呈剂量依赖性下降。氟哌啶醇和甲氧氯普胺在两组动物中的效力大致相等，而舒必利和硫利达嗪在 6-OHDA 处理的小鼠中的效力大约是 4 倍（肌肉张力减退的发生使得解释氯氮平的作用变得困难）。这些数据表明中脑边缘伏核在调节阿朴吗啡攀爬中发挥重要作用，并表明当中脑边缘机制变得“超敏感”时，舒必利和硫利达嗪的拮抗作用可能会特别增强。
Bilateral intra-accumbens 6-OHDA (2 μg in the presence of DMI and tranylcypromine, 14th postoperative day) enhanced the climbing responses of mice to apomorphine and 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin causing parallel shifts of the normal log dose-response curves to the left. The enhancement of the apomorphine response was shown to be dependent on the dose of 6-OHDA, 0.5 μg being threshold and 2 μg maximum. Increased climbing was apparent by the 5th postoperative day, maximum by the 10th day, and was then maintained throughout the experimental period (6–8 weeks). 0.25-2 μg intra-accumbens 6-OHDA caused dose-related decreases in the dopamine content of mesolimbic areas (nucleus accumbens and tuberculum olfactorium) without causing significant changes in mesolimbic noradrenaline or striatal dopamine. In the absence of DMI/tranyl-cypromine, 2 and 4 μg 6-OHDA also decreased mesolimbic noradrenaline and striatal dopamine content. 16 μg 6-OHDA injected into the striatum (after DMI/tranylcypromine) decreased the striatal dopamine content by 85% (without altering mesolimbic dopamine or noradrenaline content) but this treatment failed to modify apomorphine climbing (2nd–12th postoperative days). Haloperidol, sulpiride, thioridazine, clozapine and metoclopramide each caused a dose-dependent decrease in apomorphine climbing in both normal and 6-OHDA-treated mice. Haloperidol and metoclopramide were approximately equipotent in both groups of animals whilst sulpiride and thioridazine were approximately 4× more potent in the 6-OHDA-treated mice (the development of muscular hypotonia made an interpretation of clozapine effects difficult). The data indicate an important role for the mesolimbic nucleus accumbens in the mediation of apomorphine climbing, and indicate that the antagonism by sulpiride and thioridazine may be specifically increased when mesolimbic mechanisms are rendered ‘supersensitive’.