Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders
Karel Pacák and
Miklós Palkovits
Pediatric and Reproductive Endocrinology Branch (K.P.), National
Institute of Child Health and Human Development and Clinical
Neurocardiology Section (K.P.), National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda,
Maryland; Laboratory of Genetics (M.P.), National Institute of Mental
Health, National Institutes of Health, Bethesda, Maryland 20892-1583;
and Laboratory of Neuromorphology, Semmelweis University, 1094
Budapest, Hungary (M.P.)
Despite the fact that many research articles have been written
aboutstress and stress-related diseases, no scientifically accepted
definitionof stress exists. Selye introduced and popularized stress as
amedical and scientific idea. He did not deny the existence of
stressor-specificresponse patterns; however, he emphasized that such
responsesdid not constitute stress, only the shared nonspecific
component.In this review we focus mainly on the similarities and
differencesbetween the neuroendocrine responses (especially the
sympathoadrenaland the sympathoneuronal systems and the
hypothalamo-pituitary-adrenocorticalaxis) among various stressors and
a strategy for testing Selye’sdoctrine of nonspecificity. In our
experiments, we used fivedifferent stressors: immobilization,
hemorrhage, cold exposure,pain, or hypoglycemia. With the exception of
immobilizationstress, these stressors also differed in their
intensities.Our results showed marked heterogeneity of neuroendocrine
responsesto various stressors and that each stressor has a
neurochemical"signature." By examining changes of Fos
immunoreactivity invarious brain regions upon exposure to different
stressors,we also attempted to map central stressor-specific
neuroendocrinepathways. We believe the existence of stressor-specific
pathwaysand circuits is a clear step forward in the study of the
pathogenesisof stress-related disorders and their proper treatment.
Finally,we define stress as a state of threatened homeostasis
(physicalor perceived treat to homeostasis). During stress, an
adaptivecompensatory specific response of the organism is activatedto
sustain homeostasis. The adaptive response reflects the activationof
specific central circuits and is genetically and constitutionally
programmedand constantly modulated by environmental factors.
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