title: Ceftriaxone, a beta-lactam antibiotic, attenuates relapse-like ethanol-drinking behavior in alcohol-preferring rats.
abstract: Relapse-like ethanol-drinking behavior depends on increased glutamate transmission in the mesocorticolimbic motive circuit. Extracellular glutamate is regulated by a number of glutamate transporters. Of these transporters, glutamate transporter 1 (GLT1) is responsible for the majority of extracellular glutamate uptake. We have recently reported that ceftriaxone (CEF) treatment (i.p.), a β-lactam antibiotic known to elevate GTL1 expression, reduced ethanol intake in male alcohol-preferring (P) rats. We investigated here whether CEF treatment attenuates relapse-like ethanol-drinking behavior. P rats were exposed to free choice of 15% and 30% ethanol for 5 weeks and treated with CEF (50 and 100 mg/kg, i.p.) during the last 5 days of the 2-week deprivation period. Rats treated with CEF during the deprivation period showed a reduction in ethanol intake compared with saline-treated rats upon re-exposure to ethanol; this effect persisted for 9 days. Moreover, CEF-mediated attenuation in relapse to ethanol-drinking behavior was associated with upregulation of GLT1 level in prefrontal cortex and nucleus accumbens core. GLT1 upregulation was revealed only at the higher dose of CEF. In addition, CEF has no effect on relapse-like sucrose-drinking behavior. These findings suggest that ceftriaxone might be used as a potential therapeutic treatment for the attenuation of relapse-like ethanol-drinking behavior.
authors.affiliation: Department of Pharmacology, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Qrunfleh
authors.forename: Adnan
authors.initials: A
authors.lastname: Alazizi
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000428:Alcohol Drinking / Q000517:prevention & control*; D000818:Animals; D002443:Ceftriaxone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics*; D007274:Injections, Intraperitoneal; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D055502:Secondary Prevention; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D000431:Ethanol; D013395:Sucrose; D002443:Ceftriaxone
keywords: EAAT2; Relapse; alcohol dependence; ethanol intake; glutamate