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Neurochemical and behavioral study on the relationship between depression and alcohol and cocaine dependence in mice: influence of the cannabinoid system

Grant number: 09/01270-6
Support type:Regular Research Grants
Duration: June 01, 2009 - November 30, 2011
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Dartiu Xavier da Silveira
Grantee:Dartiu Xavier da Silveira
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Substance dependence is a chronic disease with great impact in public health. High comorbidity with other medical conditions leads to worse the prognosis making the treatment of the addictive disorder even more difficult. Although there is a considerable amount of knowledge on the neurobiological mechanisms involved in the disorders separately, the intrinsic mechanisms of the associated conditions still remain unclear. Learning and memory play an important role in the development of substance dependence. From the neurobiological point of view, CREB phosphorylation (in response to AMPc binding) and consequently BDNF expression (brain derived neurotrophic factor) and delta FosB, as well as endocannabinoid system modulation, are events that share common mechanisms in depression, substance dependence, and learning and memory processes. Aiming at verifying neurochemical and behavioral consequences of depression on associative learning induced by drugs, this study will investigate if moderate chronic stress (animal model of depression) is able to modify ethanol and cocaine induced place preference. Furthermore, through immunohistochemical studies, it will be evaluated CREB, phosphorilated CREB, BDNF, Delta FosB, aiming at identifying neurochemical mechanisms involved in possible behavioral alterations observed in place preference testing. Considering the importance of the endocannabinoid system, it will be investigated if the antidepressant effect due to pharmacological manipulation is able to revert neurochemical and behavioral alterations of memory and learning processes due to chronic stress. Additionally it will be evaluated the immune reactivity of CB1 e CB2 receptors. (AU)