Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders

The development of new treatments for substance use disorders requires identification of targetable molecular mechanisms. Pathology in glutamatergic neurotransmission system in brain reward circuitry has been implicated in relapse to multiple classes of drugs. Glutamate transporter 1 (GLT-1) crucial...

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Bibliographic Details
Published inCNS & neurological disorders drug targets Vol. 14; no. 6; p. 745
Main Authors Roberts-Wolfe, Douglas J, Kalivas, Peter W
Format Journal Article
LanguageEnglish
Published United Arab Emirates 01.01.2015
Subjects
Acetylcysteine - pharmacology
Acetylcysteine - therapeutic use
Animals
Ceftriaxone - pharmacology
Ceftriaxone - therapeutic use
Excitatory Amino Acid Transporter 2 - metabolism
Glutamic Acid - metabolism
Humans
Neurotransmitter Uptake Inhibitors - therapeutic use
Substance-Related Disorders - therapy
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Summary:The development of new treatments for substance use disorders requires identification of targetable molecular mechanisms. Pathology in glutamatergic neurotransmission system in brain reward circuitry has been implicated in relapse to multiple classes of drugs. Glutamate transporter 1 (GLT-1) crucially regulates glutamatergic signaling by removing excess glutamate from the extrasynaptic space. The purpose of this review is to highlight the effects of addictive drug use on GLT-1 and glutamate uptake, and using GLT-1 as a target in addiction pharmacotherapy. Cocaine, opioids, ethanol, nicotine, amphetamines, and cannabinoids each affect GLT-1 expression and glutamate uptake, and restoring GLT-1 expression with N-acetylcysteine or ceftriaxone shows promise in correcting pre-clinical and clinical manifestations of drug addiction.
ISSN:1996-3181
DOI:10.2174/1871527314666150529144655