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Am J Physiol Regul Integr Comp Physiol 275: R1247-R1255, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 4, R1247-R1255, October 1998

Heterogeneous neurochemical responses to different stressors: a test of Selye's doctrine of nonspecificity

Karel Pacak1,2, Miklos Palkovits3, Gal Yadid4, Richard Kvetnansky5, Irwin J. Kopin1, and David S. Goldstein1

1 Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke and 3 Laboratory of Cell Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892; 2 Department of Medicine, Washington Hospital Center, Washington, District of Columbia 20010; 4 Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel 52100; and 5 Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic 81000

Selye defined stress as the nonspecific response of the body to any demand. Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary responses. One can test Selye's concept by comparing magnitudes of responses at different stress intensities and assuming that the magnitudes vary with stress intensity, with the prediction that, at different stress intensities, ratios of increments neuroendocrine responses should be the same. We measured arterial plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage, intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization. Relative to ACTH increments, cold evoked large norepinephrine responses, insulin large epinephrine responses, and hemorrhage small norepinephrine and epinephrine responses, whereas immobilization elicited large increases in levels of all three compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%, and the epinephrine response to 25% hemorrhage was two times that to 10%. The ACTH response to 4% formaldehyde solution was two times that to 1%, and the epinephrine response to 4% formaldehyde solution exceeded four times that to 1%. These results are inconsistent with Selye's doctrine of nonspecificity and the existence of a unitary "stress syndrome," and they are more consistent with the concept that each stressor has its own central neurochemical and peripheral neuroendocrine "signature."

ACTH; norepinephrine; epinephrine


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