Serial exposure to ethanol drinking and methamphetamine enhances glutamate excitotoxicity

Amanda L. Blaker, Elizabeth R. Moore, Bryan K. Yamamoto

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


A significant comorbidity exists between alcohol and methamphetamine (Meth) abuse but the neurochemical consequences of this co-abuse are unknown. Alcohol and Meth independently and differentially affect glutamatergic transmission but the unique effects of their serial exposure on glutamate signaling in mediating damage to dopamine neurons are unknown. Sprague–Dawley rats had intermittent voluntary access to 10% ethanol (EtOH) every other day and water over 28 days and were then administered a binge injection regimen of Meth or saline. EtOH drinking decreased the glutamate aspartate transporter and increased basal extracellular concentrations of glutamate within the striatum when measured after the last day of drinking. Ceftriaxone is known to increase the expression and/or activity of glutamate transporters in the brain and prevented both the decreases in glutamate aspartate transporter and the increases in basal extracellular glutamate when administered during EtOH drinking. EtOH drinking also exacerbated the acute increases in extracellular glutamate observed upon Meth exposure, the subsequent increases in spectrin proteolysis, and the long-term decreases in dopamine content in the striatum, all of which were attenuated by ceftriaxone administration during EtOH drinking only. These results implicate EtOH-induced increases in extracellular glutamate and corresponding decreases in glutamate uptake as mechanisms that contribute to the vulnerability produced by EtOH drinking and the unique neurotoxicity observed after serial exposure to Meth that is not observed with either drug alone. (Figure presented.). Open Science: This manuscript was awarded with the Open Materials Badge. For more information see:

Original languageEnglish (US)
Pages (from-to)749-763
Number of pages15
JournalJournal of Neurochemistry
Issue number6
StatePublished - Dec 1 2019


  • alcohol
  • dopamine
  • excitotoxicity
  • glutamate
  • methamphetamine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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