Glutamate transport: A new bench to bedside mechanism for treating drug abuse

Sade Spencer, Peter W. Kalivas

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

Abstract

Drug addiction has often been described as a "hijacking" of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past 20 years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior. Much of this research focuses on the role played by ionotropic glutamate receptors directly involved in long-Term potentiation and depression or metabotropic receptors indirectly modulating synaptic plasticity. Importantly, the balance between glutamate release and clearance tightly regulates the patterned activation of these glutamate receptors, emphasizing an important role for glutamate transporters in maintaining extracellular glutamate levels. Five excitatory amino acid transporters participate in active glutamate reuptake. Recent evidence suggests that these glutamate transporters can be modulated by chronic drug use at a variety of levels. In this review, we synopsize the evidence and mechanisms associated with drug-induced dysregulation of glutamate transport. We then summarize the preclinical and clinical data suggesting that glutamate transporters offer an effective target for the treatment of drug addiction. In particular, we focus on the role that altered glutamate transporters have in causing drug cues and contexts to develop an intrusive quality that guides maladaptive drug seeking behaviors.

Original languageEnglish (US)
Pages (from-to)797-812
Number of pages16
JournalInternational Journal of Neuropsychopharmacology
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institute on Drug Abuse at the National Institutes of Health (DA003906, DA012513, DA015369 to P.W.K. and DA041462 to S.S.) and the Burroughs Wellcome Fund (1012607).

Keywords

  • Addiction
  • Cellular redox
  • Glutamate transporters
  • N-Acetylcysteine
  • Relapse

Fingerprint Dive into the research topics of 'Glutamate transport: A new bench to bedside mechanism for treating drug abuse'. Together they form a unique fingerprint.

Cite this