ArticlePloS one2012
Loop diuretics have anxiolytic effects in rat models of conditioned anxiety.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- Effects of low doses of the novel dehydroepiandrosterone (DHEA) derivative BNN27 in rat models of anxiety.Psychopharmacology · 2024Article
- Antihypertensive drugs and brain function: mechanisms underlying therapeutically beneficial and harmful neuropsychiatric effects.Cardiovascular research · 2023Review
- Cardiovascular therapeutics: A new potential for anxiety treatment?Medicinal research reviews · 2022Review
- The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology.Frontiers in physiology · 2022Review
- Bumetanide blocks the acquisition of conditioned fear in adult rats.British journal of pharmacology · 2018Article
- Analysis of genome-wide association data highlights candidates for drug repositioning in psychiatry.Nature neuroscience · 2017Article
- The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain.Neural plasticity · 2017Review
- Is birth a critical period in the pathogenesis of autism spectrum disorders?Nature reviews. Neuroscience · 2015Review
- Investigating the stress attenuating potential of furosemide in immobilization and electric foot-shock stress models in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Intracellular chloride accumulation: a possible mechanism for cognitive deficits in Down syndrome.Nature medicine · 2015Article
- Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases.Current neuropharmacology · 2015Review
- Pharmacotherapeutic targeting of cation-chloride cotransporters in neonatal seizures.Epilepsia · 2014Review
- Neuroinflammation and comorbidity of pain and depression.Pharmacological reviews · 2014Review
- Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat.PloS one · 2014Article
- Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy.Epilepsy & behavior : E&B · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.