Bumetanide blocks the acquisition of conditioned fear in adult rats
Autor: | Tso Hao Tang, Yi Ling Yang, Tamara G. Amstislavskaya, Meng Chang Ko, Maria A. Tikhonova, Kwok Tung Lu, Ming Chung Lee |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Pharmacology Startle response medicine.diagnostic_test medicine.drug_class business.industry Long-term potentiation Neurotransmission Anxiolytic Amygdala 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure medicine Systemic administration Fear conditioning business 030217 neurology & neurosurgery Bumetanide medicine.drug |
Zdroj: | British Journal of Pharmacology. 175:1580-1589 |
ISSN: | 0007-1188 |
DOI: | 10.1111/bph.14125 |
Popis: | 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. |
Databáze: | OpenAIRE |
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