The role played by the dorsal and median raphe nuclei in the modulation of stress and anxiety-related responses

• Grant number: 13/17389-8
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: November 30, 2015
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Milena de Barros Viana
• Grantee: Milena de Barros Viana
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Isabel Cristina Céspedes ; Liana Melo-Thomas

Abstract

The concept of stress is based on the observation that any environmental change, either external or internal, can disturb the maintenance of homeostasis/allostasis, causing a series of physiological alterations, the so-called "general adaptation syndrome". The purpose of the stress reaction is to maintain homeostasis/allostasis, which includes physiological reactions such as endocrine activation (in particular of the hypothalamus-pituitary-adrenal - HPA axis) and visceral changes, which per se, do not produce pathological consequences. Nevertheless, when the stimulation is prolonged or sustained, exceeding the body's capacity to maintain homeostasis/allostasis, stress can induce pathological sequelae. An important neurotransmitter system that seems to be altered in stress-related disorders is the serotonergic system originated from the raphe nuclei. The purpose of the present study is to investigate the role played by the dorsal and median raphe nuclei in the modulation of behavioral and physiological responses related to stress and anxiety. For that, in a first experiment, male Wistar rats will be exposed to acute (30 min restriction) or chronic stress (an unpredictable chronic mild stress protocol, for 14 days). Control animals will remain under standard laboratory conditions for the same period. Twenty-four hours after the exposure to the stressful stimuli, rats will be intra-cardiacally perfused and their brains will be removed. The number of doubly-immunostained cells for Fos protein and tryptophan hydroxylase, a marker of serotonergic neurons, will then be assessed within different subdivisions of the rat dorsal raphe nucleus and in the median raphe to compare the effects of acute and chronic stress on serotonin neurotransmission. In a second study, the effects of the stimulation of different subnuclei of the dorsal raphe, the dorsal nucleus and the lateral wings, on the behavior of animals submitted to the avoidance and escape of the elevated T-maze will be investigated through the use of Deep Brain Stimulation (DBS). Aside from this behavioral analysis, this study will also investigate the effects of DBS on Fos protein immunoreactivity in different brain regions related to defense. This study will contribute to a better understanding of the neurobiology of stress and anxiety. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

WSCIEKLICA, TATIANA; SILVA, MARIANA S. C. F.; LEMES, JESSICA A.; MELO-THOMAS, LIANA; CESPEDES, ISABEL C.; VIANA, MILENA B.. Deep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic. Behavioural Brain Research, v. 321, p. 193-200, MAR 15 2017. (13/17389-8)

LOPES, DANIELLE A.; LEMES, JESSICA A.; MELO-THOMAS, LIANA; SCHOR, HERBERT; DE ANDRADE, JOSE S.; MACHADO, CARLA M.; HORTA-JUNIOR, JOSE A. C.; CESPEDES, ISABEL C.; VIANA, MILENA B.. Unpredictable chronic mild stress exerts anxiogenic-like effects and activates neurons in the dorsal and caudal region and in the lateral wings of the dorsal raphe nucleus. Behavioural Brain Research, v. 297, p. 180-186, JAN 15 2016. (13/17389-8)

SILVA, MARIANA S. C. F.; PEREIRA, BRUNO A.; CESPEDES, ISABEL C.; NASCIMENTO, JULIANA O. G.; BITTENCOURT, JACKSON C.; VIANA, MILENA B.. Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze. Behavioural Brain Research, v. 271, p. 249-257, SEP 1 2014. (11/17471-0, 13/17389-8)

SILVA, MARIANA S. C. F.; SOUZA, THAISSA M. O.; PEREIRA, BRUNO A.; RIBEIRO, DANIEL A.; CESPEDES, ISABEL C.; BITTENCOURT, JACKSON C.; VIANA, MILENA B.. The blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape responses in the elevated T-maze. Behavioural Brain Research, v. 329, p. 41-50, JUN 30 2017. (13/17389-8)