title: Ceftriaxone treatment affects the levels of GLT1 and ENT1 as well as ethanol intake in alcohol-preferring rats.
abstract: Studies have demonstrated that deletion of equilibrative nucleoside transporter 1 (ENT1) is associated with reduced glutamate transporter 1 (GLT1) level, and consequently increased ethanol intake. In this study, we measured changes in GLT1 and ENT1 levels in prefrontal cortex (PFC), and nucleus accumbens (NAc) core and shell associated with alcohol drinking in alcohol-preferring (P) rats. We examined, then, whether ceftriaxone (CEF) would affect both GLT1 and ENT1 levels in these brain regions. P rats were given 24-h concurrent access to 15 and 30% ethanol, water, and food for 5 weeks. On Week 6, P rats received 100 mg/kg CEF (i.p.) or a saline vehicle for five consecutive days. Ethanol intake was measured daily for 8 days starting on the first day of injections. We found a significant reduction in daily ethanol intake in CEF-treated group, starting on Day 2 of injections. Western blot for GLT1 and binding assay for ENT1 revealed downregulation of GLT1 level, whereas ENT1 levels were increased in the NAc core and NAc shell, respectively, but not in the PFC in saline vehicle group. Importantly, CEF treatment reversed these effects in both NAc core and shell. These findings provide evidence for potential regulatory effects of CEF on both GLT1 and ENT1 expression in reducing ethanol intake.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, 43614, USA, youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
authors.forename: Sai N
authors.initials: SN
authors.lastname: Sreemantula
authors.forename: Moonnoh R
authors.initials: MR
authors.lastname: Lee
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism*; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D033721:Equilibrative Nucleoside Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; C438652:Slc29a1 protein, rat; D002443:Ceftriaxone
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