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Function of ventral medial pre frontal cortex on modulation of cardiovascular and respiratory responses to chemoreflex activation in anesthetized rats

Grant number: 12/01120-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2012
Effective date (End): August 31, 2012
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Leonardo Resstel Barbosa Moraes
Grantee:Erica Maria Granjeiro
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The ventral portion of the medial pre frontal cortex (vMPFC), which comprises the prelimbic cortex (PL) and the infralimbic cortex (IL), has been implicated in several aspects of cardiovascular control. Electric or chemical stimulation of the vMPFC evokes changes in blood pressure (BP) and heart rate (HR). Additionally, this brain area is connected to several limbic structures implicated in behavioral control, as well as to forebrain and brainstem structures involved in the cardiovascular control. With respect to hypoxia, it was observed an increase in c-fos protein expression, a marker of neuronal activity, in the vMPFC of rats submitted to 30 days of intermittent chronic hypoxia (Sica et al., 2000). This evidence could indicate a possible involvement of vMPFC on the neural pathway of peripheral chemoreceptors. During acute hypoxic situations, the activation of peripheral chemoreceptors in anesthetized rats leads an increase in respiratory frequency, autonomic responses, including increase in BP and decrease in HR, and a behavioral response, which consists of an initial alertness immediately followed by an exploration of the environment (Franchini & Krieger, 1992, 1993; Haibara et al. 1995, 1999). In a recent study from our laboratory (Granjeiro et al., 2011) was demonstrated that bilateral microinjections of the unspecic synaptic blocker CoCl2 into the PL cortex of anesthetized rats evoked a signicant attenuation in the pressor response to chemoreflex activation using KCN. However, no significant changes were observed in the chemoreex-induced HR decrease. These results suggest that the pressor but not the bradycardic response to chemoreex activation is, at least in part, mediated by local neurotransmission present in the PL cortex. Several neurotransmitters into the vMPFC have been reported to participate in the cardiovascular modulation; among them the glutamatergic and nitrergic systems and it seems there is a balance between these mechanisms in the cardiovascular regulation. Furthermore, studies of literature have indicated that local glutamatergic neurotransmission in the vMPFC is modulated by endocannabinoid system. So, this project aims to study the involvement of the glutamatergic, nitrergic and endocannabinoid neurotransmission in the PL and IL cortex on the cardiovascular and respiratory responses to chemoreflex activation in anesthetized rats. To achieve this purpose the chemoreex will be activated with KCN (i.v.) before and after bilateral microinjections of the glutamatergic and nitrergic antagonists into the PL and IL cortex of anesthetized rats. In addition, we will also evaluate if the local endocannabinoid-mediated neurotransmission in the vMPFC can act out the glutamatergic and nitrergic effects.