---
title: "Glibenclamide modulates monoamines and partly restores memory in a scopolamine rat model"
id: "pubmed-42155807"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42155807"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42155807/"
doi: "10.1016/j.bbr.2026.116280"
published_at: "2026-08-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Glibenclamide modulates monoamines and partly restores memory in a scopolamine rat model
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42155807
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42155807/)
- **DOI:** [10.1016/j.bbr.2026.116280](https://doi.org/10.1016%2Fj.bbr.2026.116280)
- **Published At:** 2026-08-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated chronic **glibenclamide (GD)** effects in a rat model of cholinergic dysfunction induced by **scopolamine (SCO)**. - Adult male Wistar rats were assigned to control (saline), SCO (1 mg/kg), GD (50 µg/kg), and GD+SCO groups. - Behavioral tests included the **Morris water maze (MWM)**, Y-maze, and elevated plus maze (EPM) to assess spatial learning, memory consolidation, working memory, and anxiety-like behavior. - Neurochemical analyses measured dopamine (DA), norepinephrine (NE), serotonin (5-HT) and metabolites in the **striatum** and **hippocampus** by HPLC. - Expression of monoamine-metabolizing enzymes **MAO-A**, **MAO-B**, and **COMT** was quantified using RT-qPCR. - SCO impaired spatial learning and memory in the MWM (increased AUC and reduced time in the target quadrant) but did not alter working memory or anxiety-like behavior. - GD alone increased striatal **dopamine** and improved memory consolidation, while paradoxically impairing spatial learning; GD decreased hippocampal DA. - SCO reduced hippocampal homovanillic acid (HVA) and **serotonin (5-HT)**. - Combined GD+SCO partially attenuated SCO-induced memory deficits and restored striatal 5-HT levels. - GD increased **MAO-B** mRNA in the striatum, and SCO decreased **MAO-A** mRNA in the hippocampus. - The authors conclude GD exerts **region-specific modulation** of monoaminergic systems, producing a dual profile: partial restoration of memory consolidation in SCO-treated rats but impairment of spatial learning and reduction of hippocampal monoamines. - Keywords reported include COMT, Cognitive impairment, Dopamine, Glibenclamide, Hippocampus, MAO-A, MAO-B, Monoamines, Morris water maze, Scopolamine, Serotonin, Striatum.
## Clinical Analysis & Structured Key Points
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Epub 2026 May 19. # Glibenclamide exerts region-specific modulatory effects on monoaminergic neurotransmission and partially restores memory consolidation in a scopolamine-induced model of cognitive impairment [Daria Alexeevna Obukhova](https://pubmed.ncbi.nlm.nih.gov/?term=Obukhova+DA&cauthor_id=42155807)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#full-view-affiliation-1 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia; Institute of Human Brain, N.P. Bekhtereva RAS, St. Petersburg, Russia. Electronic address: obuhowadaria@gmail.com."), [Zamira Magomedovna Muruzheva](https://pubmed.ncbi.nlm.nih.gov/?term=Muruzheva+ZM&cauthor_id=42155807)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#full-view-affiliation-2 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia; North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia."), [Margarita Timurovna Absalyamova](https://pubmed.ncbi.nlm.nih.gov/?term=Absalyamova+MT&cauthor_id=42155807)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#full-view-affiliation-3 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia."), [Marina Nikolaevna Karpenko](https://pubmed.ncbi.nlm.nih.gov/?term=Karpenko+MN&cauthor_id=42155807)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#full-view-affiliation-3 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia.") Affiliations Expand ### Affiliations * 1 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia; Institute of Human Brain, N.P. Bekhtereva RAS, St. Petersburg, Russia. Electronic address: obuhowadaria@gmail.com. * 2 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia; North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia. * 3 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia. * PMID: **42155807** * DOI: [ 10.1016/j.bbr.2026.116280 ](https://doi.org/10.1016/j.bbr.2026.116280) Item in Clipboard # Glibenclamide exerts region-specific modulatory effects on monoaminergic neurotransmission and partially restores memory consolidation in a scopolamine-induced model of cognitive impairment Daria Alexeevna Obukhova et al. Behav Brain Res. 2026. Show details Display options Display options Format Abstract PubMed PMID Behav Brain Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Behav+Brain+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Behav+Brain+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42155807/) . 2026 Aug 5:511:116280. doi: 10.1016/j.bbr.2026.116280. Epub 2026 May 19. ### Authors [Daria Alexeevna Obukhova](https://pubmed.ncbi.nlm.nih.gov/?term=Obukhova+DA&cauthor_id=42155807)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#short-view-affiliation-1 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia; Institute of Human Brain, N.P. Bekhtereva RAS, St. Petersburg, Russia. Electronic address: obuhowadaria@gmail.com."), [Zamira Magomedovna Muruzheva](https://pubmed.ncbi.nlm.nih.gov/?term=Muruzheva+ZM&cauthor_id=42155807)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#short-view-affiliation-2 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia; North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia."), [Margarita Timurovna Absalyamova](https://pubmed.ncbi.nlm.nih.gov/?term=Absalyamova+MT&cauthor_id=42155807)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#short-view-affiliation-3 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia."), [Marina Nikolaevna Karpenko](https://pubmed.ncbi.nlm.nih.gov/?term=Karpenko+MN&cauthor_id=42155807)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42155807/#short-view-affiliation-3 "Department of Physiology \(Pavlov's\), Institute of Experimental Medicine, St. Petersburg, Russia.") ### Affiliations * 1 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia; Institute of Human Brain, N.P. Bekhtereva RAS, St. Petersburg, Russia. Electronic address: obuhowadaria@gmail.com. * 2 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia; North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia. * 3 Department of Physiology (Pavlov's), Institute of Experimental Medicine, St. Petersburg, Russia. * PMID: **42155807** * DOI: [ 10.1016/j.bbr.2026.116280 ](https://doi.org/10.1016/j.bbr.2026.116280) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Cognitive impairment from cholinergic dysfunction is a hallmark of neurodegenerative and age-related disorders. Scopolamine (SCO), a muscarinic acetylcholine receptor antagonist, is widely used to model such deficits in animals. Glibenclamide (GD), a sulfonylurea used to treat type 2 diabetes, has been proposed to possess neuroprotective properties. **Objective:** This study evaluated behavioral and neurochemical effects of chronic GD administration in a rat model of SCO-induced cognitive impairment. **Methods:** Adult male Wistar rats were divided into four groups: control (saline), SCO (1 mg/kg), GD (50 µg/kg), and GD+SCO. Behavioral assessments included the Morris water maze (MWM), Y-maze, and elevated plus maze (EPM). Monoamine levels (DA, NE, 5-HT and metabolites) in the striatum and hippocampus were measured by HPLC, and expression of monoamine-metabolizing enzymes (MAO-A, MAO-B, COMT) analyzed via RT-qPCR. **Results:** SCO impaired spatial learning and memory (increased AUC and reduced time in the MWM target quadrant) without affecting working memory or anxiety-like behavior. GD alone increased striatal DA and improved memory consolidation, although spatial learning was impaired. In the hippocampus, GD decreased DA, while SCO reduced HVA and 5-HT. Combined GD and SCO partly moderated SCO-induced memory deficits and restored striatal 5-HT. GD elevated MAO-B mRNA in the striatum, whereas SCO reduced MAO-A in the hippocampus. **Conclusion:** GD modulates monoaminergic systems region-specifically under cholinergic dysfunction. While it partly restores memory consolidation in SCO-treated rats, it also impairs learning and decreases hippocampal monoamines. These findings highlight a complex, dual role of GD, improving memory consolidation while impairing spatial learning through region-specific modulation of monoaminergic systems. **Keywords:** COMT; Cognitive impairment; Dopamine; Glibenclamide; Hippocampus; MAO-A; MAO-B; Monoamines; Morris water maze; Scopolamine; Serotonin; Striatum. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Pioglitazone improves learning and memory in a rat model of cholinergic dysfunction induced by scopolamine, the roles of oxidative stress and neuroinflammation. ](https://pubmed.ncbi.nlm.nih.gov/39960561/) Rajabian A, Kioumarsi Darbandi Z, Aliyari M, Saberi R, Amirahmadi S, Amini H, Salmani H, Youseflee P, Hosseini M.Rajabian A, et al.Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug;398(8):10221-10237. doi: 10.1007/s00210-025-03895-5. Epub 2025 Feb 17.Naunyn Schmiedebergs Arch Pharmacol. 2025.PMID: 39960561 * [ Treatment with soybean lecithin-derived α-GPC (SHCog™) improves scopolamine-induced cognitive declines in mice via regulating cholinergic neurotransmission and enhancing neural plasticity in the hippocampus. ](https://pubmed.ncbi.nlm.nih.gov/39765138/) Zheng Y, An S, Kim GY, Park GD, Yoo BH, Kim KN, Lee TK.Zheng Y, et al.Tissue Cell. 2025 Apr;93:102705. doi: 10.1016/j.tice.2024.102705. 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