Effects of purinergic drugs on the emotional memory and attention of an animal model of Schizophrenia

• Grant number: 13/15717-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2013
• Effective date (End): October 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Mariana Bendlin Calzavara
• Grantee: Bianca Avansi Camerini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Our group recently described that the SHR strain (spontaneouly hipertensive rats) shows a deficit in the task of contextual fear conditioning (a model for the study of emotional processing), which is specifically reversed by antipsychotics (drugs used in the treatment of schizophrenia) and augmented by manipulations related to worsening schizophrenia. Furthermore, this strain has a deficit in latent inhibition test, another widely used paradigm to study attentional deficits present in schizophrenia. Losses in processing emotions and attention underlie schizophrenia and have been suggested as a factor for the onset of severe symptoms associated with this disease. However, there have been few efforts to investigate the neurobiological basis of these abnormalities in emotion processing. Specifically in this project, we intend to extend and deepen the characterization of the deficit of contextual fear conditioning. More specifically, we will evaluate the involvement of the purinergic system to acquire the task of contextual fear conditioning and latent inhibition by administration of papaverine, an inhibitor of the enzyme phosphodiesterase 10A; caffeine, an antagonist of A2a adenosine type A1 and GSC 21680, an A2a agonist. Recent works have shown an antipsychotic profile of papaverine, since the end neurochemical effect is similar to that in the administration of antipsychotics, ie the increase in adenosine monophosphate (AMP).This project is part of a research arm of the Interdisciplinary Laboratory of Clinical Neurosciences (LINC), coordinated by prof. Dr. Rodrigo A. Bressan, Department of Psychiatry of this University, in which Dr Mariana B. Calzavara acts as researcher and advisor. This partnership aims to develop translational approaches, undoubtedly enriching the both basic and clinical research on the pathophysiology and treatment of psychiatric disorders. In this sense, the development of this project is a preliminary step to assess the involvement of different aspects of purinergic neurotransmission in animal models with the future goal of extending the results to studies in patients with schizophrenia. Thus, this project is part of a broader line of research and pioneering that we believe have much to contribute to both clinical and basic understanding of psychiatric disorders. The project has the equipments and support of approved projects on behalf of the guideline and those in which there is collaboration with Prof. Dr. Vanessa C. Abilio, member of LinC and faculty member of the Department of Pharmacology of UNIFESP.