Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.

A number of antiepileptic medications that modulate GABA(A) mediated synaptic transmission are anxiolytic. The loop diuretics furosemide (Lasix) and bumetanide (Bumex) are thought to have antiepileptic properties. These drugs also modulate GABA(A) mediated signalling through their antagonism of cati...

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Autores principales:	Andrew D Krystal, Janice Sutherland, Daryl W Hochman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/690b3496b49341e2a3acaa3e98a2bfdd
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spelling	oai:doaj.org-article:690b3496b49341e2a3acaa3e98a2bfdd2021-11-18T07:22:09ZLoop diuretics have anxiolytic effects in rat models of conditioned anxiety.1932-620310.1371/journal.pone.0035417https://doaj.org/article/690b3496b49341e2a3acaa3e98a2bfdd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514741/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A number of antiepileptic medications that modulate GABA(A) mediated synaptic transmission are anxiolytic. The loop diuretics furosemide (Lasix) and bumetanide (Bumex) are thought to have antiepileptic properties. These drugs also modulate GABA(A) mediated signalling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signalling, we sought to investigate whether they also mediate anxiolytic effects. Here we report the first investigation of the anxiolytic effects of these drugs in rat models of anxiety. Furosemide and bumetanide were tested in adult rats for their anxiolytic effects using four standard anxiety models: 1) contextual fear conditioning; 2) fear-potentiated startle; 3) elevated plus maze, and 4) open-field test. Furosemide and bumetanide significantly reduced conditioned anxiety in the contextual fear-conditioning and fear-potentiated startle models. At the tested doses, neither compound had significant anxiolytic effects on unconditioned anxiety in the elevated plus maze and open-field test models. These observations suggest that loop diuretics elicit significant anxiolytic effects in rat models of conditioned anxiety. Since loop diuretics are antagonists of the NKCC1 and KCC2 cotransporters, these results implicate the cation-chloride cotransport system as possible molecular mechanism involved in anxiety, and as novel pharmacological target for the development of anxiolytics. In view of these findings, and since furosemide and bumetanide are safe and well tolerated drugs, the clinical potential of loop diuretics for treating some types of anxiety disorders deserves further investigation.Andrew D KrystalJanice SutherlandDaryl W HochmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35417 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrew D Krystal Janice Sutherland Daryl W Hochman Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
description	A number of antiepileptic medications that modulate GABA(A) mediated synaptic transmission are anxiolytic. The loop diuretics furosemide (Lasix) and bumetanide (Bumex) are thought to have antiepileptic properties. These drugs also modulate GABA(A) mediated signalling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signalling, we sought to investigate whether they also mediate anxiolytic effects. Here we report the first investigation of the anxiolytic effects of these drugs in rat models of anxiety. Furosemide and bumetanide were tested in adult rats for their anxiolytic effects using four standard anxiety models: 1) contextual fear conditioning; 2) fear-potentiated startle; 3) elevated plus maze, and 4) open-field test. Furosemide and bumetanide significantly reduced conditioned anxiety in the contextual fear-conditioning and fear-potentiated startle models. At the tested doses, neither compound had significant anxiolytic effects on unconditioned anxiety in the elevated plus maze and open-field test models. These observations suggest that loop diuretics elicit significant anxiolytic effects in rat models of conditioned anxiety. Since loop diuretics are antagonists of the NKCC1 and KCC2 cotransporters, these results implicate the cation-chloride cotransport system as possible molecular mechanism involved in anxiety, and as novel pharmacological target for the development of anxiolytics. In view of these findings, and since furosemide and bumetanide are safe and well tolerated drugs, the clinical potential of loop diuretics for treating some types of anxiety disorders deserves further investigation.
format	article
author	Andrew D Krystal Janice Sutherland Daryl W Hochman
author_facet	Andrew D Krystal Janice Sutherland Daryl W Hochman
author_sort	Andrew D Krystal
title	Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
title_short	Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
title_full	Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
title_fullStr	Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
title_full_unstemmed	Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
title_sort	loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/690b3496b49341e2a3acaa3e98a2bfdd
work_keys_str_mv	AT andrewdkrystal loopdiureticshaveanxiolyticeffectsinratmodelsofconditionedanxiety AT janicesutherland loopdiureticshaveanxiolyticeffectsinratmodelsofconditionedanxiety AT darylwhochman loopdiureticshaveanxiolyticeffectsinratmodelsofconditionedanxiety
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Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.

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