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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