Local neurochemical mechanisms involved in the control of cardiovascular responses to restraint stress by different regions of the posterior portion of the insular cortex in rats

• Grant number: 22/03070-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2022
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Ricardo Luiz Nunes de Souza
• Grantee: Adrielly dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The survival of species in the face of aversive events or stressors depends on a coordinated set of physiological and behavioral responses. The insular cortex (IC) is a cortical structure that has been implicated in the integration and processing of limbic information in humans and animals. In fact, it has been reported an involvement of the iC in the generation of physiological and behavioral responses during stressful situations. The IC is divided into anterior and posterior portions, and the posterior portion is further sub-divided into rostral, intermediate and caudal. A recent study by our group explored the participation of different regions along the rostro-caudal axis of the IC in the control of cardiovascular responses to restraint stress in rats. This study identified that non-selective synaptic blockade of the IC anterior region did not affect the cardiovascular responses to acute restraint stress. However, in the posterior portion, this block caused site-specific effects. The synaptic inhibition at rostral sites of the posterior IC reduced the pressor response, while blocking sites in the caudal region of the posterior IC reduced the tachycardiac response. In turn, neuronal activation along the rostrocaudal axis of the IC was also evaluated. In this sense, it was identified that the control of the tachycardiac response by the caudal subregion of the posterior IC was associated with a decrease in the number of Fos-positeve cells, which indicated a reduction in neuronal activation. On the other hand, control of the pressor response by the rostral subregion of the posterior portion of the IC was accompanied by an increase in Fos-positive cells. These data provided evidence that the control of cardiovascular responses to stress by the rostral and caudal subregions of the posterior portion of the IC might be mediated by different neurochemical mechanisms. From these data, our hypothesis is that the control of pressor responses to stress by the rostral region of the posterior IC is mediated mainly by the activation of excitatory neurochemical mechanisms, whereas the involvement of the caudal region in the tachycardic response involves the recruitment of local inhibitory mechanisms. In this sense, previous studies identified the presence of glutamatergic neurotransmission, the main excitatory neurotransmitter in the central nervous system (CNS), in the IC. Besides, it was reported an important role of glutamatergic mechanisms in different sites of the IC in the control of cardiovascular function under rest conditions. Whereas, GABA, the main inhibitory neurotransmitter in the CNS, has been reported to play a tonic inhibitory role via activation of the GABAA receptor in the posterior region of the IC in the maintenance of mean arterial pressure (MAP) and sympathetic activity in rats in rest. However, an involvement of glutamatergic and GABAergic mechanisms of IC in the control of cardiovascular responses to stress has never been evaluated. Thus, the present study will aim to 1) to investigate the effect of bilateral microinjection of glutamatergic and GABAergic receptor antagonists into the rostral and caudal regions of the posterior portion of the IC on cardiovascular responses to acute restraint stress; and 2) to evaluate the effect of bilateral microinjection of glutamatergic and GAbaergic receptor antagonists into the rostral and caudal regions of the posterior IC on changes in the number of local Fos-positive cells induced by restraint stress.