Serial exposure to ethanol drinking and methamphetamine enhances glutamate excitotoxicity

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

Research output: Contribution to journalArticle

Abstract

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. Open science badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. (Figure presented.).

Original languageEnglish (US)
JournalJournal of Neurochemistry
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Methamphetamine
Drinking
Glutamic Acid
Ethanol
Amino Acid Transport System X-AG
Ceftriaxone
Dopamine
Alcohols
Proteolysis
Spectrin
Manuscripts
Dopaminergic Neurons
Disclosure
Alcoholism
Neurons
Comorbidity
Rats
Brain
Injections
Water

Keywords

  • alcohol
  • dopamine
  • excitotoxicity
  • GLAST
  • glutamate
  • methamphetamine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Serial exposure to ethanol drinking and methamphetamine enhances glutamate excitotoxicity. / Blaker, Amanda L.; Moore, Elizabeth R.; Yamamoto, Bryan K.

In: Journal of Neurochemistry, 01.01.2019.

Research output: Contribution to journalArticle

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