title: Metabotropic and ionotropic glutamate receptors as potential targets for the treatment of alcohol use disorder.
abstract: Emerging evidence indicates that dysfunctional glutamate neurotransmission is critical in the initiation and development of alcohol and drug dependence. Alcohol consumption induced downregulation of glutamate transporter 1 (GLT-1) as reported in previous studies from our laboratory. Glutamate is the major excitatory neurotransmitter in the brain, which acts via interactions with several glutamate receptors. Alcohol consumption interferes with the glutamatergic signal transmission by altering the functions of these receptors. Among the glutamate receptors involved in alcohol-drinking behavior are the metabotropic receptors such as mGluR1/5, mGluR2/3, and mGluR7, as well as the ionotropic receptors, NMDA and AMPA. Preclinical studies using agonists and antagonists implicate these glutamatergic receptors in the development of alcohol use disorder (AUD). Therefore, the purpose of this review is to discuss the neurocircuitry involving glutamate transmission in animals exposed to alcohol and further outline the role of metabotropic and ionotropic receptors in the regulation of alcohol-drinking behavior. This review provides ample information about the potential therapeutic role of glutamatergic receptors for the treatment of AUD.
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA; The Neurodegeneration Consortium, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Goodwani
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Saternos
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Alasmari
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000437:Alcoholism; D000438:Alcohols; D000818:Animals; D018698:Glutamic Acid; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate; D009435:Synaptic Transmission
chemical_list: D000438:Alcohols; D058468:Receptors, Ionotropic Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: AMPA; Alcohol; Glutamate; NMDA; mGluR1/5; mGluR2/3; mGluR7