title: Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model.
abstract: Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4 g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48 h of withdrawal, P rats were re-exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States.
authors.forename: Sujan C
authors.initials: SC
authors.lastname: Das
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States.
authors.forename: Yusuf S
authors.initials: YS
authors.lastname: Althobaiti
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States.
authors.forename: Fahad S
authors.initials: FS
authors.lastname: Alshehri
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, United States. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D027182:Amino Acid Transport System y+
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D015306:Biogenic Monoamines; D004298:Dopamine; D000431:Ethanol; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005974:Glutamate-Ammonia Ligase; D018698:Glutamic Acid; D005973:Glutamine; D012701:Serotonin; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; C000723960:Slc7a11 protein, rat; D027182:Amino Acid Transport System y+
keywords: Binge ethanol; Dopamine; GLT-1; Glutamate; Glutamine synthetase
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