Glutamate and modeling of schizophrenia symptoms: review of our findings: 1990-2014.

Pharmacol Rep

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.

Published: June 2014

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pharep.2014.03.010DOI Listing

Publication Analysis

Top Keywords

schizophrenia symptoms
8
affective levels
8
glutamatergic transmission
8
disturbances
6
schizophrenia
5
glutamate modeling
4
modeling schizophrenia
4
symptoms review
4
review findings
4
findings 1990-2014
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!