Investigation of brain structures involved in pre-pulse inhibition and social interaction deficits in an animal model of schizophrenia - the SHR strain

• Grant number: 11/15539-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): February 28, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Mayra Akimi Suiama
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia is the most serious mental illnesses and the dopaminergic system is classically associated with the pathophysiology and therapeutic effects of antipsychotics. Although it is a complex pathology, the use of good animal models can provide important contributions to the understanding of the pathophysiology of this disorder and for the development and improvement of therapeutic strategies.Recently we suggested that the SHR strain of mice can be used as a good model for the study of schizophrenia. Accordingly, we find that the deficit in the task of fear conditioning to the context presented by the line (suggested by us as a model for the study of losses in processing emotional information - Calzavara et al. 2009; 2011th) is attenuated by increased neuronal activity (promoted by the administration of veratridin by increasing the activity of sodium channels voltage-gated - Singewald et al., 2000) or by injection of D1 agonist in the prefrontal cortex. Likewise, this deficit is also mitigated by the decrease in neuronal activity (promoted by the administration of tetrodotoxin, to block sodium channels voltage-gated-Lorenzini et al., 1995) or injection of antagonist of D2 receptors in the nucleus accumbens. These data are consistent with the hypofunction of the prefrontal cortex via D1 receptors and increased dopamine transmission in the nucleus accumbens via dopamine D2 receptors associated with the pathophysiology of schizophrenia. In this project we intend to extend the characterization of the involvement of brain structures (nucleus accumbens and prefrontal cortex) and its neuronal activity and dopamine transmission to two other behavioral changes observed in the line: the deficit of PPI (the model for the study of poor operation of the filter in schizophrenia sensorimotor) and the lack of social interaction (model for the study of negative symptoms of schizophrenia).