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

Author(s): Douglas J. Roberts-Wolfe, Peter W. Kalivas.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 14 , Issue 6 , 2015

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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.

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Article Details

VOLUME: 14
ISSUE: 6
Year: 2015
Page: [745 - 756]
Pages: 12
DOI: 10.2174/1871527314666150529144655
Price: $65

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