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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Fingerprint

Bumetanide
Fear
Amygdala
Startle Reflex
Anti-Anxiety Agents
Sodium Potassium Chloride Symporter Inhibitors
Long-Term Potentiation
Locomotion
Anxiety Disorders
Synaptic Transmission
Wistar Rats
Western Blotting
Phosphorylation

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

Bumetanide blocks the acquisition of conditioned fear in adult rats. / Ko, Meng Chang; Lee, Ming Chung; Tang, Tso Hao; Amstislavskaya, Tamara G.; Tikhonova, Maria A.; Yang, Yi Ling; Lu, Kwok Tung.

In: British Journal of Pharmacology, Vol. 175, No. 10, 01.05.2018, p. 1580-1589.

Research output: Contribution to journalArticle

Ko, MC, Lee, MC, Tang, TH, Amstislavskaya, TG, Tikhonova, MA, Yang, YL & Lu, KT 2018, 'Bumetanide blocks the acquisition of conditioned fear in adult rats', British Journal of Pharmacology, vol. 175, no. 10, pp. 1580-1589. https://doi.org/10.1111/bph.14125
Ko MC, Lee MC, Tang TH, Amstislavskaya TG, Tikhonova MA, Yang YL et al. Bumetanide blocks the acquisition of conditioned fear in adult rats. British Journal of Pharmacology. 2018 May 1;175(10):1580-1589. https://doi.org/10.1111/bph.14125
Ko, Meng Chang ; Lee, Ming Chung ; Tang, Tso Hao ; Amstislavskaya, Tamara G. ; Tikhonova, Maria A. ; Yang, Yi Ling ; Lu, Kwok Tung. / Bumetanide blocks the acquisition of conditioned fear in adult rats. In: British Journal of Pharmacology. 2018 ; Vol. 175, No. 10. pp. 1580-1589.
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