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

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)