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The effects of FLUOXETIN and deep brain stimulation applied to different subnuclei of the dorsal raphe on the behavior of rats in the elevated T-maze and on serotonergic and GABAergic neurotransmission

Grant number: 18/10530-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Humanities - Psychology - Physiological Psychology
Principal Investigator:Milena de Barros Viana
Grantee:Mariana Santos Carvalho de Faria Silva
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil


Previous results obtained using Deep Brain Stimulation (DBS) applied to the dorsal portion of the dorsal raphe nucleus (DDR) and to the lateral wings (alDRN) of the same structure in rats showed anxiolytic-like effects of DRD stimulation and panicolytic-like effects of the stimulation of the alDRN in the elevated T-maze model (ETM). In addition, the DBS technique also increased c-Fos protein expression in anxiety-related prosencephalic regions, such as the prefrontal cortex, the medial amygdala, and the lateral septum. The aim of the present study was to better investigate the nature of the anxiolytic and panicolytic-like effects of DBS. For that, in a first study it will be verified whether the chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, used in clinical practice as an anxiolytic and panicolytic agent, increases the effects of DBS in the ETM. In addition, the neurochemical identity of the activated cells in the different sub-regions of the dorsal raphe nucleus will be investigated through double-labeled for the c-Fos protein and the enzyme tryptophan hydroxylase (Trp-OH), the limiting enzyme which participates in serotonin synthesis. Since there is some controversy in the literature on whether neurons of the alDRN are serotonergic or GABAergic, we will also conduct a double-labeled immunohistochemistry study for the c-Fos protein and for glutamate decarboxylase, the rate-limiting enzyme which regulates GABA synthesis. Both of these immunohistochemistry studies will be performed in response to DBS administration alone, and in response to the combined treatment with fluoxetine and DBS.