Bumetanide blocks the acquisition of conditioned fear in adult rats

Meng Chang Ko, Ming Chung Lee, Tso Hao Tang, Tamara G. Amstislavskaya, Maria A. Tikhonova, Yi Ling Yang*, Kwok Tung Lu

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

3 引文 斯高帕斯(Scopus)

摘要

Background and Purpose: Bumetanide has anxiolytic effects in rat models of conditioned fear. As a loop diuretic, bumetanide blocks cation–chloride co-transport and this property may allow bumetanide to act as an anxiolytic by modulating GABAergic synaptic transmission in the CNS. Its potential for the treatment of anxiety disorders deserves further investigation. In this study, we evaluated the possible involvement of the basolateral nucleus of the amygdala in the anxiolytic effect of bumetanide. Experimental Approach: Brain slices were prepared from Wistar rats. extracellular recording, stereotaxic surgery, fear-potentiated startle response, locomotor activity monitoring and Western blotting were applied in this study. Key Results: Systemic administration of bumetanide (15.2 mg·kg −1 , i.v.), 30 min prior to fear conditioning, significantly inhibited the acquisition of the fear-potentiated startle response. Phosphorylation of ERK in the basolateral nucleus of amygdala was reduced after bumetanide administration. In addition, suprafusion of bumetanide (5 or 10 μM) attenuated long-term potentiation in the amygdala in a dose-dependent manner. Intra-amygdala infusion of bumetanide, 15 min prior to fear conditioning, also blocked the acquisition of the fear-potentiated startle response. Finally, the possible off-target effect of bumetanide on conditioned fear was excluded by side-by-side control experiments. Conclusions and Implications: These results suggest the basolateral nucleus of amygdala plays a critical role in the anxiolytic effects of bumetanide.

原文英語
頁(從 - 到)1580-1589
頁數10
期刊British Journal of Pharmacology
175
發行號10
DOIs
出版狀態已發佈 - 2018 五月 1

ASJC Scopus subject areas

  • 藥理

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