The tail of the Ventral Tegmental Area (tVTA) as a new neurostructural target for schizophrenia's pathophysiology: an animal model study - the SHR rat strain

• Grant number: 13/21619-9
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2014
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Raí Álvares Eufrásio
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia is a highly disabling mental disorder with great impact to our society. Its onset happens between late adolescence and early adulthood, brings severe impairments in cognitive and social performances, as well as great suffering to the patients and their family. The pathophysiology of schizophrenia, although not completely elucidated, is associated to an increased dopaminergic neurotransmission in the mesolimbic pathway - neurons originating in the Ventral Tegmental Area (VTA) and projecting to limbic structures - and a decreased dopaminergic transmission in the mesocortical pathway - neurons originating in the VTA and projecting to the prefrontal cortex. The therapy is carried out with antipsychotic drugs which, although represent an important progress in psychopharmacology, don't treat satisfactorily all individuals. Therefore, advances in elucidating the pathophysiology of this disease are necessary not only to better understand the processes underling its symptomatology but also to develop new treatments. In this sense, a new mesopontine neurostructure was recently described that exerts an inhibitory control over the dopaminergic transmission originating in the VTA and Substantia Nigra: the tail of the Ventral Tegmental Area / Rostromedial Tegmental Nucleus (tVTA / RMTg). Bearing in mind the close relationship between tVTA functioning and dopaminergic pathways related to schizophrenia, studying its contribution to the disease is of great relevance. Thus, this project aims to evaluate the effects of tVTA neural activation or inactivation (by means of local injections of µ-opioid receptor agonist DAMGO or antagonist CTOP, respectively) on the behavioral alterations shown by the SHR rat strain, suggested by our group as a good animal model to study various aspects of schizophrenia.