title: Glutamate and Brain Glutaminases in Drug Addiction.
abstract: Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain. marquez@uma.es.|Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. marquez@uma.es.
authors.forename: Javier
authors.identifier: http://orcid.org/0000-0003-3317-3963
authors.initials: J
authors.lastname: Márquez
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Campos-Sandoval
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Peñalver
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Matés
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Segura
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, IBIMA, Hospital Regional Universitario, 29010, Málaga, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Canceromics Lab, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071, Málaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alonso
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, IBIMA, Hospital Regional Universitario, 29010, Málaga, Spain.
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: de Fonseca
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism; D050356:Lipid Metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D013287:Illicit Drugs; D007527:Isoenzymes; D018698:Glutamic Acid; D005972:Glutaminase
keywords: Cocaine; Drugs of abuse; Glutamate; Glutamatergic neuroadaptations; Glutaminase; Synaptic plasticity