Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders

Abstract

Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

“…Stress has been described as a potential threat, arising from outside or from within the organism [128,120], and has also been defined operationally as a physiological or psychological threat that activates the 'stress-response' machinery [108]. Stress triggers molecular cascades that allow rapid behavioral, autonomic and cognitive CNS responses to stressful circumstances, followed by prompt re-establishment of functional steady-state.…”

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…While this is conceivable, it is unclear how such 'systemic' effects alone could have produced the regionally selective molecular changes in the sensorimotor striatum. Moreover, according to previous studies, striatal regions (and midbrain dopamine neurons) display relatively minor or no c-fos induction by stressors (for reviews, see Senba and Ueyama, 1997;Kovacs, 1998;Pacak and Palkovits, 2001). Also, stress was ruled out as a major contributor to striatal c-fos induction during treadmill running (Liste et al, 1997).…”

The hypothalamic-pituitary-adrenal axis in anxiety and panic.

“…As a result, they have defined stress as a state of threatened homeostasis (physical or perceived threat to homeostasis) that triggers stimulus-specific adaptive compensatory responses. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors (Pacák & Palkovits, 2001). This view may help to understand the seeming paradox on panic attacks and the HPA axis that is discussed in the following section.…”