title: Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions.
abstract: Studies have shown that administration of the β-lactam antibiotic ceftriaxone (CEF) attenuates ethanol consumption and cocaine seeking behavior as well as prevents ethanol-induced downregulation of glutamate transporter 1 (GLT-1) expression in central reward brain regions. However, it is not known if these effects are compound-specific. Therefore, the present study examined the effects of two other β-lactam antibiotics, amoxicillin (AMOX) and amoxicillin/clavulanate (Augmentin, AUG), on ethanol drinking, as well as GLT-1 and phosphorylated-AKT (pAKT) levels in the nucleus accumbens (Acb) and medial prefrontal cortex (mPFC) of alcohol-preferring (P) rats. P rats were exposed to free-choice of ethanol (15% and 30%) for five weeks and were given five consecutive daily i.p. injections of saline vehicle, 100 mg/kg AMOX or 100mg/kg AUG. Both compounds significantly decreased ethanol intake and significantly increased GLT-1 expression in the Acb. AUG also increased GLT-1 expression in the mPFC. Results for changes in pAKT levels matched those for GLT-1, indicating that β-lactam antibiotic-induced reductions in ethanol intake are negatively associated with increases in GLT-1 and pAKT levels within two critical brains regions mediating drug reward and reinforcement. These findings add to a growing literature that pharmacological increases in GLT-1 expression are associated with decreases in ethanol intake and suggest that one mechanism mediating this effect may be increased phosphorylation of AKT. Thus, GLT-1 and pAKT may serve as molecular targets for the treatment of alcohol and drug abuse/dependence.
authors.affiliation: The University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Goodwani
authors.affiliation: The University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, USA.
authors.forename: P S S
authors.initials: PS
authors.lastname: Rao
authors.affiliation: Department of Psychiatry and Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.affiliation: The University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000427:Alcohol Deterrents / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism; D000658:Amoxicillin / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D014867:Water / Q000008:administration & dosage
chemical_list: D000427:Alcohol Deterrents; D000900:Anti-Bacterial Agents; D002492:Central Nervous System Depressants; D019422:Dietary Sucrose; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D014867:Water; D000431:Ethanol; D002443:Ceftriaxone; D000658:Amoxicillin; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Amoxicillin; Augmentin; Clavulanate; GLT-1