title: Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders.
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.
authors.affiliation: Department of Neuroscience, Medical University of So Carolina, 173 Ashley Ave, BSB403, Charleston, SC 29425, USA. roberdj@musc.edu.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Roberts-Wolfe
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kalivas
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D019966:Substance-Related Disorders / Q000628:therapy*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D014179:Neurotransmitter Uptake Inhibitors; D018698:Glutamic Acid; D002443:Ceftriaxone; D000111:Acetylcysteine