title: Targeting glutamate homeostasis for potential treatment of nicotine dependence.
abstract: Several studies demonstrated that impairment in glutamatergic neurotransmission is linked to drug dependence and drug-seeking behavior. Increased extracellular glutamate concentration in mesocorticolimbic regions has been observed in animals developing nicotine dependence. Changes in glutamate release might be associated with stimulatory effect of nicotinic acetylcholine receptors (nAChRs) via nicotine exposure. We and others have shown increased extracellular glutamate concentration, which was associated with down regulation of the major glutamate transporter, glutamate transporter 1 (GLT-1), in brain reward regions of animals exposed to drug abuse, including nicotine and ethanol. Importantly, studies from our laboratory and others showed that upregulation of GLT-1 expression in the mesocorticolimbic brain regions may have potential therapeutic effects in drug dependence. In this review article, we discussed the effect of antagonizing presynaptic nAChRs in glutamate release, the upregulatory effect in GLT-1 expression and the role of glutamate receptors antagonists in the treatment of nicotine dependence.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA.
authors.forename: Fawaz
authors.initials: F
authors.lastname: Alasmari
authors.affiliation: Department of Pharmacology and Toxicology, King Saud University, College of Pharmacy, Riyadh, Saudi Arabia.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al-Rejaie
authors.affiliation: Department of Pharmacology and Toxicology, King Saud University, College of Pharmacy, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Shakir D
authors.initials: SD
authors.lastname: AlSharari
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000628:therapy*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D009538:Nicotine
keywords: GLT-1; Nicotine; iGLURs; mGluRs; nAChRs; xCT