دورية أكاديمية
Effects of MC-100093 on Ethanol Drinking and the Expression of Astrocytic Glutamate Transporters in the Mesocorticolimbic Brain Regions of Male and Female Alcohol-Preferring Rats.
العنوان: | Effects of MC-100093 on Ethanol Drinking and the Expression of Astrocytic Glutamate Transporters in the Mesocorticolimbic Brain Regions of Male and Female Alcohol-Preferring Rats. |
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المؤلفون: | Alotaibi A; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA., Travaglianti S; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA., Wong W; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA., Abou-Gharbia M; Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA., Childers W; Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA., Sari Y; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA. Electronic address: youssef.sari@utoledo.edu. |
المصدر: | Neuroscience [Neuroscience] 2024 Aug 06; Vol. 552, pp. 89-99. Date of Electronic Publication: 2024 Jun 22. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605074 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7544 (Electronic) Linking ISSN: 03064522 NLM ISO Abbreviation: Neuroscience Subsets: MEDLINE |
أسماء مطبوعة: | Publication: [New York?] : Elsevier Science Original Publication: Oxford, Elmsford, N. Y., Pergamon Press |
مواضيع طبية MeSH: | Alcohol Drinking*/metabolism , Astrocytes*/metabolism , Astrocytes*/drug effects , Excitatory Amino Acid Transporter 2*/metabolism , Excitatory Amino Acid Transporter 2*/biosynthesis , Ethanol*/administration & dosage , Ethanol*/pharmacology , Nucleus Accumbens*/metabolism , Nucleus Accumbens*/drug effects, Animals ; Female ; Male ; Rats ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/drug effects ; Central Nervous System Depressants/pharmacology ; Central Nervous System Depressants/administration & dosage ; Sex Characteristics |
مستخلص: | Chronic ethanol consumption increased extracellular glutamate concentrations in several reward brain regions. Glutamate homeostasis is regulated in majority by astrocytic glutamate transporter 1 (GLT-1) as well as the interactive role of cystine/glutamate antiporter (xCT). In this study, we aimed to determine the attenuating effects of a novel beta-lactam MC-100093, lacking the antibacterial properties, on ethanol consumption and GLT-1 and xCT expression in the subregions of nucleus accumbens (NAc core and NAc shell) and medial prefrontal cortex (Infralimbic, mPFC-IL and Prelimbic, mPFC-PL) in male and female alcohol-preferring (P) rats. Female and male rats were exposed to free access to ethanol (15% v/v) and (30% v/v) and water for five weeks, and on Week 6, rats were administered 100 mg/kg (i.p) of MC-100093 or saline for five days. MC-100093 reduced ethanol consumption in both male and female P rats from Day 1-5. Additionally, MC-100093 upregulated GLT-1 and xCT expression in the mPFC and NAc subregions as compared to ethanol-saline groups in female and male rats. Chronic ethanol intake reduced GLT-1 and xCT expression in the IL and PL in female and male rats, except there was no reduction in GLT-1 expression in the mPFC-PL in female rats. Although, MC-100093 upregulated GLT-1 and xCT expression in the subregions of NAc, we did not observe any reduction in GLT-1 and xCT expression with chronic ethanol intake in female rats. These findings strongly suggest that MC-100093 treatment effectively reduced ethanol intake and upregulated GLT-1 and xCT expression in the mPFC and NAc subregions in male and female P rats. Competing Interests: Declaration of interest statement The authors declare that they have no financial interests or personal relationships in the work reported in this research article. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
معلومات مُعتمدة: | R01 AA029674 United States AA NIAAA NIH HHS |
فهرسة مساهمة: | Keywords: GLT-1; ethanol dependence; glutamate; nucleus accumbens; xCT |
المشرفين على المادة: | 0 (Excitatory Amino Acid Transporter 2) 3K9958V90M (Ethanol) 0 (Slc1a2 protein, rat) 0 (Central Nervous System Depressants) |
تواريخ الأحداث: | Date Created: 20240623 Date Completed: 20240728 Latest Revision: 20240728 |
رمز التحديث: | 20240729 |
DOI: | 10.1016/j.neuroscience.2024.06.017 |
PMID: | 38909675 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-7544 |
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DOI: | 10.1016/j.neuroscience.2024.06.017 |