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As a loop diuretic, bumetanide blocks cation\u2013chloride co\u2010transport 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Brain slices were prepared from Wistar rats. extracellular recording, stereotaxic surgery, fear\u2010potentiated startle response, locomotor activity monitoring and Western blotting were applied in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Systemic administration of bumetanide (15.2\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v.), 30\u00a0min prior to fear conditioning, significantly inhibited the acquisition of the fear\u2010potentiated startle response. Phosphorylation of ERK in the basolateral nucleus of amygdala was reduced after bumetanide administration. In addition, suprafusion of bumetanide (5 or 10\u00a0\u03bcM) attenuated long\u2010term potentiation in the amygdala in a dose\u2010dependent manner. Intra\u2010amygdala infusion of bumetanide, 15\u00a0min prior to fear conditioning, also blocked the acquisition of the fear\u2010potentiated startle response. Finally, the possible off\u2010target effect of bumetanide on conditioned fear was excluded by side\u2010by\u2010side control experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results suggest the basolateral nucleus of amygdala plays a critical role in the anxiolytic effects of bumetanide.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14125","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T03:04:42Z","timestamp":1513134282000},"page":"1580-1589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bumetanide blocks the acquisition of conditioned fear in adult rats"],"prefix":"10.1111","volume":"175","author":[{"given":"Meng\u2010Chang","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Life Science National Taiwan Normal University  Taipei 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