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Evaluation of left and right medial prefrontal cortex glutamatergic and GABAergic neurotransmissions in ethanol-induced consumption by social defeat stress in mice

Grant number: 16/08665-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2017
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Cleopatra da Silva Planeta
Grantee:Lucas Canto de Souza
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):18/05808-0 - Testing the role of the left and right medial prefrontal cortex in fear extinction and anxiety with optogenetic manipulations, BE.EP.PD

Abstract

The medial prefrontal cortex (mPFC) is ivolved in the modulation of different behaviors, which include those associated with the use of ethanol and response to stressors. This brain region is predominantly composed of glutamatergic neurons and GABAergic interneurons, in addition to receiving dopaminergic afferents from the ventral tegmental area. Recently, it has been proposed that the mPFC functions can be lateralized, such that the left mPFC (LmPFC) may have inhibitory control over the right mPFC (RmPFC). An animal model that can be used to investigate the effect of stress on the ethanol consumption is the social defeat. However, to observe an increase of ethanol consumption, previous studies demonstrated that are necessary at least 30 bites in five minutes over 10 days. According to the evidence that the increase in ethanol consumption is observed after a long period of social defeat (chronic stress), and functional lateralization of the mPFC in the control of emotional states, the hypothesis of this study is that during the first contacts with the stressor, the LmPFC inhibits RmPFC, which fails to occur after a long period of social defeat, resulting in an increase of ethanol consumption. To test this hypothesis, the present study will investigate: the effects of momentary inhibition of left or right mPFC through the local injection of cobalt chloride (CoCl2), on ethanol intake in mice subjected to acute stress session of social defeat (Experiment 1); the expression of Fos protein in the mPFC by immunohistochemistry technique in mice subjected to social defeat (Experiment 2); to identify the involvement of L and R mPFC glutamatergic and gabaergic mechanisms, this study will investigate (double labeling immunofluorescence) the pattern of neuronal activation protein Fos + neurotransmission by glutamate (CamKII) and GABA (GAD67) in mice subjected to social defeat (Experiment 3) and the involvement of glutamatergic and GABAergic neurotransmission in the dorso medial portion of the L and R mPFC in ethanol consumption induced by the stress of social defeat, through intra-mPFC injections on L or R glutamate (AP-7) and GABAergic (bicuculline) antagonists (experiment 4). (AU)

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