Effects of ceftriaxone on ethanol, nicotine or sucrose intake by alcohol-preferring (P) rats and its association with GLT-1 expression

Youssef Sari, Jamie E. Toalston, P. S.S. Rao, Richard L. Bell

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Increased glutamatergic neurotransmission appears to mediate the reinforcing properties of drugs of abuse, including ethanol (EtOH). We have shown that administration of ceftriaxone (CEF), a β-lactam antibiotic, reduced EtOH intake and increased glutamate transporter 1 (GLT-1) expression in mesocorticolimbic regions of male and female alcohol-preferring (P) rats. In the present study, we tested whether CEF administration would reduce nicotine (NIC) and/or EtOH intake by adult female P rats. P rats were randomly assigned to 4 groups: (a) 5% sucrose (SUC) or 10% SUC [SUC], (b) 5% SUC + 0.07 mg/ml NIC and 10% SUC + 0.14 mg/ml NIC [NIC-SUC], 15% EtOH and 30% EtOH [EtOH] and (d) 15% EtOH + 0.07 mg/ml NIC and 30% EtOH + 0.14 mg/ml NIC [NIC-EtOH]. After achieving stable intakes (4 weeks), the rats were administered 7 consecutive, daily i.p. injections of either saline or 200 mg/kg CEF. The effects of CEF on intake were significant but differed across the reinforcers; such that ml/kg/day SUC was reduced by ~30%, mg/kg/day NIC was reduced by ~70% in the NIC-SUC group and ~40% in the EtOH-NIC group, whereas g/kg/day EtOH was reduced by ~40% in both the EtOH and EtOH-NIC group. The effects of CEF on GLT-1 expression were also studied. We found that CEF significantly increased GLT-1 expression in the prefrontal cortex and the nucleus accumbens of the NIC and NIC-EtOH rats as compared to NIC and NIC-EtOH saline-treated rats. These findings provide further support for GLT-1-associated mechanisms in EtOH and/or NIC abuse. The present results along with previous reports of CEF's efficacy in reducing cocaine self-administration in rats suggest that modulation of GLT-1 expression and/or activity is an important pharmacological target for treating polysubstance abuse and dependence.

Original languageEnglish (US)
Pages (from-to)117-125
Number of pages9
JournalNeuroscience
Volume326
DOIs
StatePublished - Jun 21 2016

Keywords

  • Addiction
  • Alcohol
  • Ceftriaxone
  • Drinking
  • EAAT2
  • Polysubstance

ASJC Scopus subject areas

  • Neuroscience(all)

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