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Org24598, a Selective Glycine Transporter 1 (GlyT1) Inhibitor, Reverses Object Recognition and Spatial Memory Impairments Following Binge-like Ethanol Exposure in Rats.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, c1995-
    • Subject Terms:
      Glycine Plasma Membrane Transport Proteins*/antagonists & inhibitors ; Glycine Plasma Membrane Transport Proteins*/metabolism ; Ethanol* ; Receptors, N-Methyl-D-Aspartate*/metabolism ; Receptors, N-Methyl-D-Aspartate*/antagonists & inhibitors ; Rats, Wistar* ; Spatial Memory*/drug effects ; Memory Disorders*/drug therapy ; Memory Disorders*/metabolism ; Memory Disorders*/chemically induced; Animals ; Rats ; Male ; Recognition, Psychology/drug effects ; Binge Drinking/metabolism ; Binge Drinking/drug therapy ; Glycine/pharmacology ; Glycine/analogs & derivatives ; Hippocampus/metabolism ; Hippocampus/drug effects ; Piperidines/pharmacology ; Maze Learning/drug effects
    • Abstract:
      The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol, and it is implicated in learning and memory formation, and other cognitive functions. Glycine acts as a co-agonist for this receptor. We examined whether Org24598, a selective inhibitor of glycine transporter1 (GlyT1), affects ethanol withdrawal-induced deficits in recognition memory (Novel Object Recognition (NOR) task) and spatial memory (Barnes Maze (BM) task) in rats, and whether the NMDA receptor glycine site participates in this phenomenon. Male Wistar rats were habituated to NOR or BM tasks, and then received binge-like intragastric ethanol administration (5 days, 5 g/kg). After ethanol withdrawal, Org24598 (0.1, 0.3, and 0.6 mg/kg) was administered 30 min before NOR (day 10 of withdrawal) or the reversal learning phase of BM (day 11-13 of withdrawal) task. The expression of GluN1 and GluN2B subunits of NMDA receptors were measured in the perirhinal cortex (PRC) and hippocampus (HIP) after termination of NOR. In the BM task, a glycine antagonist, L-701,324 (5 mg/kg), was administered 30 min before Org24598 to confirm the involvement of the NMDA receptor glycine site in the effects of Org24598. Our study showed that binge-like ethanol administration induced recognition and spatial memory impairments after withdrawal in rats. Additionally, an up-regulation of GluN1 and GluN2B subunits of the NMDA receptor was observed in the HIP and PRC on day 11 of abstinence. Org24598 ameliorated memory loss and normalized the expression of these subunits. L-701,324 reversed the effect of Org24598. Thus, NMDA receptor glycine sites are important in ethanol withdrawal-induced memory impairments.
    • Grant Information:
      DS22/22 Medical University of Lublin
    • Contributed Indexing:
      Keywords: Barnes-maze task; Org24598; ethanol; memory; novel object recognition; withdrawal
    • Accession Number:
      0 (Glycine Plasma Membrane Transport Proteins)
      3K9958V90M (Ethanol)
      0 (Receptors, N-Methyl-D-Aspartate)
      0 (Slc6a9 protein, rat)
      TE7660XO1C (Glycine)
      0 (Piperidines)
    • Publication Date:
      Date Created: 20250108 Date Completed: 20250108 Latest Revision: 20250108
    • Publication Date:
      20250114
    • Accession Number:
      10.3390/molecules29246017
    • Accession Number:
      39770104