Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions

Sunil Goodwani, P. S.S. Rao, Richard L. Bell, Youssef Sari

Research output: Contribution to journalArticle

20 Scopus citations

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 100 mg/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.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
JournalBrain research
Volume1622
DOIs
StatePublished - Oct 5 2015

Keywords

  • AKT
  • Amoxicillin
  • Augmentin
  • Clavulanate
  • GLT-1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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