Abstract
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.
Keywords: Accumbens, addiction, ceftriaxone, excitatory amino acid transporter 2, glutamate transport, glutamate transporter 1, glutamate, N-acetylcysteine.
CNS & Neurological Disorders - Drug Targets
Title:Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders
Volume: 14 Issue: 6
Author(s): Douglas J. Roberts-Wolfe and Peter W. Kalivas
Affiliation:
Keywords: Accumbens, addiction, ceftriaxone, excitatory amino acid transporter 2, glutamate transport, glutamate transporter 1, glutamate, N-acetylcysteine.
Abstract: 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.
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Roberts-Wolfe J. Douglas and Kalivas W. Peter, Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders, CNS & Neurological Disorders - Drug Targets 2015; 14 (6) . https://dx.doi.org/10.2174/1871527314666150529144655
DOI https://dx.doi.org/10.2174/1871527314666150529144655 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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