title: Glutamate and modeling of schizophrenia symptoms: review of our findings: 1990-2014.
abstract: In the early 90s, we studied the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test in schizophrenic patients. Results were clear, showing a shape discrimination failure. Following this initial results, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, decrease in affective levels and working memory disturbances can be induced by specific N-methyl-D-aspartic acid (NMDA) glutamatergic blockade within the nucleus accumbens septi (NAS). We studied also another glutamatergic and dopaminergic drugs, finding that a decrease in glutamatergic transmission within NAS led to cognitive disturbances and affective flattening. An increase in glutamatergic transmission fully enhances cognition in the tasks used. Dopaminergic D-2 antagonists partially improved cognition. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems, but also influencing affective levels and cognitive variables. According to our translational findings, core schizophrenia symptoms may be translationally reproduced antagonizing NMDA receptors within NAS, and improved blocking the glutamate auto-receptor. Dopaminergic transmission appears to have a role in therapeutic but not in the early pathophysiology of schizophrenia.
authors.affiliation: Laboratory of Neurosciences and Experimental Psychology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Mendoza, Argentina. Argentine National Council of Scientific and Technological Research (CONICET); Area of Pharmacology, Department of Pathology, Faculty of Medical Sciences, National University of Cuyo, Ciudad Universitaria, Parque General San Martın, Mendoza, Argentina; Latin American Technological Corporation Foundation (FUCOTEL), Mendoza, Argentina. Electronic address: gargiulo@lab.cricyt.edu.ar.
authors.forename: Pascual Ángel
authors.initials: PÁ
authors.lastname: Gargiulo
authors.affiliation: Laboratory of Neurosciences and Experimental Psychology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Mendoza, Argentina. Argentine National Council of Scientific and Technological Research (CONICET); Area of Pharmacology, Department of Pathology, Faculty of Medical Sciences, National University of Cuyo, Ciudad Universitaria, Parque General San Martın, Mendoza, Argentina; Latin American Technological Corporation Foundation (FUCOTEL), Mendoza, Argentina.
authors.forename: Adriana Inés
authors.initials: AI
authors.lastname: Landa De Gargiulo
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: Affective flattening; Glutamate; Perception; Schizophrenia; Working memory