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

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Abstract

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.

Original languageEnglish
Pages (from-to)1580-1589
Number of pages10
JournalBritish Journal of Pharmacology
Volume175
Issue number10
DOIs
Publication statusPublished - 2018 May 1

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ASJC Scopus subject areas

  • Pharmacology

Cite this

Ko, M. C., Lee, M. C., Tang, T. H., Amstislavskaya, T. G., Tikhonova, M. A., Yang, Y. L., & Lu, K. T. (2018). Bumetanide blocks the acquisition of conditioned fear in adult rats. British Journal of Pharmacology, 175(10), 1580-1589. https://doi.org/10.1111/bph.14125