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Effects of sarcosine - a glycine transporter inhibitor - on an animal model of schizophrenia: the SHR (Spontaneously Hypertensive Rats) strain

Grant number: 11/12825-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2011
Effective date (End): September 30, 2012
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Vanessa Costhek Abílio
Grantee:Douglas Albuquerque Gouvêa
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia among psychiatric illness, is considered the most severe, affecting 1% of the world population. It is characterized by a framework of positive symptoms such as delusions and hallucinations, negative symptoms such as blunted affect and alogia, and cognitive deficits.Although the pathophysiology of schizophrenia is not fully established, clinical evidence from studies in animal models indicate a hypofunction of glutamatergic NMDA receptors as an important factor for the development and manifestation of this disease. In this sense, glycine modulation of this receptor is essential for its function. Thus, drugs that increase the availability of glycine are suggested as potential therapeutic agents. However, few studies have investigated the effect of these drugs on schizophrenia.Recently, our group suggested that the SHR strain has behavioral changes consistent as an animal model of schizophrenia. A deficit in the contextual fear conditioning (which reflects impairment in the processing of emotional contexts), a deficit in pre-pulse inhibition (related to dysfunction of the sensory-motor gating on schizophrenia), an increase in locomotion (associated with positive symptoms of schizophrenia) and a decrease in social interaction (associated with negative symptoms of schizophrenia) were observed in this strain and specifically reversed by administration of antipsychotics. In this context, the objective of this work is to evaluate the effect of sarcosine - a glycine transporter inhibitor - on these behavioral alterations presented by SHR. We believe that a possible beneficial effect of this agent can enhance its use in the treatment of schizophrenia.

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