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Vol. 58, No. 1, 1993
Issue release date: 1993
Neuroendocrinology 1993;58:57–64

Short Inescapable Stress Produces Long-Lasting Changes in the Brain-Pituitary-Adrenal Axis of Adult Male Rats

van Dijken H.H. · de Goeij D.C. · Sutanto W. · Mos J. · de Kloet E.R. · Tilders F.J.H.
aDepartment of Pharmacology, Medical Faculty, Free University, Amsterdam; bDivision of Medical Pharmacology, Center of Bio-Pharmaceutical Sciences, University of Leiden; cCNS Pharmacology, Solvay Duphar B.V., Weesp, The Netherlands

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Recently, we reported that rats exposed to a single and short session of inescapable footshocks showed alterations in behavioural response to environmental stimuli which developed progressively over a week and remained present for at least 28 days. The aim of the present study was to investigate whether these behavioural changes were accompanied by alterations in the brain-pituitary-adrenal axis. Male Wistar rats were subjected to 10 inescapable footshocks (S) of 6 s duration and 1 mA intensity during a period of 15 min. Control rats (C) were placed in the shock apparatus for 15 min without receiving shocks. The effects of these experimental procedures were studied 14 days later. Exposure to shocks did not affect basal plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). However, the novelty-induced ACTH response was increased in S rats as compared to C rats whereas the CORT response did not differ between C and S rats. The ACTH content of the anterior pituitary gland and adrenal weight were not affected by exposure to inescapable footshocks 14 days earlier. Quantitative immunocytochemistry of vasopressin (AVP) and corticotropin-releasing factor (CRF) in the external zone of the median eminence showed that prior footshock exposure increased the AVPi stores to 167% as compared to C rats, whereas CRFi content was not changed. In addition, S rats showed increased mineralocorticoid (MR) and glucocorticoid (GR) receptor binding capacity in the hippocampus as compared to C rats, whereas affinities were not affected. We conclude that a single and short session of inescapable footshocks has long-lasting effects on brain-pituitary-adrenal functioning concomitant with behavioural alterations.

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