Role of Glutamate Transport in Alcohol Withdrawal

Osama A Abulseoud, Christina L. Ruby, Victor Karpyak

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Glutamate is the major excitatory neurotransmitter in the brain. However, excessive glutamate can lead to neurotoxicity. Evidence suggests that a hyperglutamatergic brain state is the core pathology behind alcohol withdrawal syndrome (AWS). This hyperglutamatergic state results from upregulation of glutamate receptors, dysregulation of glutamate metabolism, and reduction of synaptic glutamate clearance. Numerous genetic factors along this pathway could modulate the vulnerability or severity of AWS. Benzodiazepines, which facilitate inhibitory neurotransmission, are standard therapeutic agents for acute AWS. While effective in reducing withdrawal severity, benzodiazepines carry risks of sedation, respiratory suppression, and dependence, and they do not correct the persistent hyperglutamatergic state associated with relapse. Data show that ceftriaxone, a β-lactam antibiotic, upregulates excitatory amino acid transporter 2 (EAAT2) and attenuates withdrawal manifestations in preclinical models. These findings underscore the importance of glutamatergic mechanisms in AWS and suggest that glutamate reuptake may represent a novel target for acute withdrawal and relapse prevention.

Original languageEnglish (US)
Title of host publicationNeuropathology of Drug Addictions and Substance Misuse Volume 1
Subtitle of host publicationFoundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids
PublisherElsevier
Pages466-477
Number of pages12
ISBN (Electronic)9780128002131
ISBN (Print)9780128003763
DOIs
StatePublished - Jan 1 2016

Keywords

  • Alcohol withdrawal
  • Ceftriaxone
  • Excitatory amino acid transporter
  • Glutamate
  • Prefrontal cortex
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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