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准吗啡戒断行为:γ-氨基丁酸能神经末梢区特定参与的指征。

Quasi-morphine withdrawal behaviour: indication for a specific involvement of the GABA-ergic nerve terminal compartment.

作者信息

van der Laan J W

出版信息

Life Sci. 1983;33 Suppl 1:389-92. doi: 10.1016/0024-3205(83)90524-6.

DOI:10.1016/0024-3205(83)90524-6
PMID:6420629
Abstract

Wet-dog-shaking resembling morphine withdrawal behaviour can be evoked in rats by administration of dipropylacetate (DPA). It has been postulated that DPA elicits the withdrawal like behaviour through specifically inhibiting the GABA-degradation in nerve terminals. Inhibition of GABA-transaminase (GABA-T) by aminooxyacetic acid (AOAA) in other compartments of the brain would result in an inhibition of the stimulated GABA-release via feedback on autoreceptors and therefore suppress the DPA-evoked behaviour. This hypothesis has been tested using the GABA-T inhibitors gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVG) and ethanolamine-O-sulphate (EOS). Although GAG and AOAA were found to suppress the body shakes, both GVG and EOS had no effect. Both GAG and AOAA have possibly also effect on glutamate decarboxylase (GAD) whereas GVG and EOS did not affect this enzyme, suggesting a nerve terminal-specific effect on DPA-induced behaviour. GVG stimulated DPA-evoked body shakes after 36 and 60 h, when a specific GABA-increase in nerve terminals will be present.

摘要

给大鼠注射二丙基乙酸(DPA)可诱发类似湿狗抖毛的吗啡戒断行为。据推测,DPA通过特异性抑制神经末梢中的γ-氨基丁酸(GABA)降解来引发类似戒断的行为。在大脑的其他区域,氨基氧乙酸(AOAA)抑制GABA转氨酶(GABA-T)会通过对自身受体的反馈抑制受刺激的GABA释放,从而抑制DPA诱发的行为。本研究使用GABA-T抑制剂γ-乙炔基-GABA(GAG)、γ-乙烯基-GABA(GVG)和乙醇胺-O-硫酸盐(EOS)对这一假说进行了验证。虽然发现GAG和AOAA可抑制身体抖动,但GVG和EOS均无此作用。GAG和AOAA可能还对谷氨酸脱羧酶(GAD)有影响,而GVG和EOS不影响该酶,这表明对DPA诱导行为存在神经末梢特异性作用。在36小时和60小时后,当神经末梢中GABA特异性增加时,GVG会刺激DPA诱发的身体抖动。

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