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[促甲状腺激素释放激素(TRH):在单侧纹状体损伤动物中增强多巴胺依赖性转圈行为及其自身的转圈诱导作用(作者译)]

[Thyrotropin-releasing hormone (TRH): Enhancement of dopamine dependent circling behavior and its own circling-inducing effect in unilateral striatal lesioned animals (author's transl)].

作者信息

Fukuda N, Miyamoto M, Narumi S, Nagai Y, Shima T, Nagawa Y

出版信息

Nihon Yakurigaku Zasshi. 1979 Apr 20;75(3):251-70. doi: 10.1254/fpj.75.251.

Abstract

Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals.

摘要

研究了促甲状腺激素释放激素(TRH)对多巴胺(DA)激动剂诱导的转圈行为的增强作用以及TRH自身对转圈行为的影响。TRH(2.5 - 20毫克/千克,腹腔注射)显著增强了由阿扑吗啡或左旋多巴诱导的转圈行为,这些小鼠通过注射6-羟基多巴胺(6-OHDA)或进行组织抽吸并随后给予利血平处理,使其单侧尾状核受损。TRH还增强了利血平化正常小鼠中阿扑吗啡诱导的刻板行为。上述TRH对转圈行为的增强作用可被α-甲基-对酪氨酸(α-MT)或GABA能药物增强、抑制或不受影响。在用TRH处理的6-OHDA损伤小鼠中,来自损伤侧而非完整侧的纹状体切片中,DA或阿扑吗啡诱导的环磷酸腺苷(cAMP)形成明显增强。在通过6-OHDA单侧损伤黑质纹状体DA通路的大鼠中,腹腔注射高剂量的TRH(100毫克/千克)或向未损伤的尾状核注射(50微克)会导致向损伤侧转圈,这一行为可被氟哌啶醇或α-MT抑制。TRH(10^(-5) - 10^(-3)摩尔/升)在体外增加了大鼠纹状体切片中14C-DA的释放。这些结果表明,低剂量的TRH在DA受体超敏状态下,通过增加纹状体中DA刺激的cAMP形成来促进DA突触后传递,高剂量时还通过增加纹状体神经末梢的DA释放来增强DA神经元活性。

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