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Pharmacological Role of Glutamate Transporters in Substance Use Disorders

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Glutamate and Neuropsychiatric Disorders

Abstract

Substance use disorders (SUD) represent a public health crisis worldwide. The development of effective pharmacotherapeutics to treat drug abuse and addiction requires the identification of targetable neurobiological mechanisms. As the primary excitatory neurotransmitter in the brain glutamate possesses a significant role in plasticity, learning, and memory, and represents a promising neurotransmitter of focus for intervention in the etiology of SUDs. Chronic drug exposure induces lasting neuroadaptations in the glutamatergic system specifically within the mesocorticolimbic (MCL) reward pathway which is posited to generate maladaptive deficits in behavioral-control, thus contributing to the addictive cycle. Maintaining the strict control of glutamate release and clearance is required for homeostasis as well as the prevention of neurotoxicity and oxidative stress. There are five excitatory amino acid transporters (EAATs) and three vesicular glutamate transporters. These function to preserve homeostatic levels of glutamate under normal physiological conditions. This review aims to highlight and summarize the preclinical evidence for dysregulation of glutamate transport following drug exposure. Additionally, alterations in glutamate transporters, with an emphasis on glutamate transporter 1 (EAAT2 encodes by SLC1A2) and its role in the development of detrimental drug-seeking behaviors, as well as current glutamate transporter-associated treatments being investigated are discussed.

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  1. Gerald A. Deehan Jr and Robert A. Waeiss contributed equally with all other contributors.

Authors and Affiliations

  1. Department of Psychology, East Tennessee State University, Johnson City, TN, USA

    Gerald A. Deehan Jr

  2. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    Robert A. Waeiss, Zachary A. Rodd, Richard L. Bell & Sheketha R. Hauser

  3. Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Robert A. Waeiss, Zachary A. Rodd, Richard L. Bell & Sheketha R. Hauser

  4. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Tiebing Liang

  5. Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA

    Youssef Sari

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Deehan, G.A. et al. (2022). Pharmacological Role of Glutamate Transporters in Substance Use Disorders. In: Pavlovic, Z.M. (eds) Glutamate and Neuropsychiatric Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-87480-3_14

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