ArticleBiological psychiatry2011
Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces excessive alcohol intake in rats.
Article in Biological psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 72 citations in OpenAlex.
- Mechanism of SK2 channel gating and its modulation by the bee toxin apamin and small molecules.eLife · 2025Article
- Pharmacological Actions of Potassium Channel Openers on Voltage-Gated Potassium Channels.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Activation of anoctamin-1 calcium-activated chloride channels reduces voluntary alcohol consumption in rats.Neuropharmacology · 2025Article
- KAlcohol (Fayetteville, N.Y.) · 2025Article
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- Influence of Inherited Seizure Susceptibility on Intermittent Voluntary Alcohol Consumption and Alcohol Withdrawal Seizures in Genetically Epilepsy-Prone Rats (GEPR-3s).Brain sciences · 2024Article
- Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.Brain communications · 2024Article
- Modeling methamphetamine use disorder and relapse in animals: short- and long-term epigenetic, transcriptional., and biochemical consequences in the rat brain.Neuroscience and biobehavioral reviews · 2023Review
- Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.Translational psychiatry · 2023Article
- Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model.bioRxiv : the preprint server for biology · 2023Article
- A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.Scientific reports · 2023Article
- Chronic Alcohol Dysregulates Glutamatergic Function in the Basolateral Amygdala in a Projection-and Sex-Specific Manner.Frontiers in cellular neuroscience · 2022Article
- Potassium Channels and Their Potential Roles in Substance Use Disorders.International journal of molecular sciences · 2021Review
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Bioinformatics identification and pharmacological validation of Kcnn3/KTranslational psychiatry · 2020Article
- A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens.Molecular neurobiology · 2020Article
- Altered Activity of SK Channel Underpins Morphine Withdrawal Relevant Psychiatric Deficiency in Infralimbic to Accumbens Shell Pathway.Frontiers in psychiatry · 2019Article
- Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence.Molecular psychiatry · 2017Article
- Stroke triggers nigrostriatal plasticity and increases alcohol consumption in rats.Scientific reports · 2017Article
- Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models.Pharmacogenomics · 2017Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlcoholism imposes a tremendous social and economic burden. There are relatively few pharmacological treatments for alcoholism, with only moderate efficacy, and there is considerable interest in identifying additional therapeutic options. Alcohol exposure alters SK-type potassium channel (SK) function in limbic brain regions. Thus, positive SK modulators such as chlorzoxazone (CZX), a US Food and Drug Administration-approved centrally acting myorelaxant, might enhance SK function and decrease neuronal activity, resulting in reduced alcohol intake.
methodsWe examined whether CZX reduced alcohol consumption under two-bottle choice (20% alcohol and water) in rats with intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In addition, we used ex vivo electrophysiology to determine whether SK inhibition and activation can alter firing of nucleus accumbens (NAcb) core medium spiny neurons.
resultsChlorzoxazone significantly and dose-dependently decreased alcohol but not water intake in IAA rats, with no effects in CAA rats. Chlorzoxazone also reduced alcohol preference in IAA but not CAA rats and reduced the tendency for rapid initial alcohol consumption in IAA rats. Chlorzoxazone reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and greater CZX inhibition of firing in IAA versus CAA rats.
conclusionsThe potent CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more moderate intake in CAA rats, might reflect the greater CZX reduction in IAA NAcb core firing observed ex vivo. Thus, CZX could represent a novel and immediately accessible pharmacotherapeutic intervention for human alcoholism.
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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.