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The Ontogeny of Glucocorticoid Negative Feedback: Influence of Maternal Deprivation¹

Department of Psychology, University of Delaware, Newark, Delaware 19716-2577; and the Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, 2300 RA Leiden, The Netherlands

Address all correspondence and requests for reprints to: E. R. de Kloet, Ph.D., Leiden/Amsterdam Center for Drug Research, Division of Medical Pharmacology, Sylvius Laboratories, P.O. Box 9503, 2300 RA Leiden, The Netherlands. E-mail: e.kloet{at}lacdr.leidenuniv.nl

Glucocorticoid feedback can be viewed as having two modes of operation: proactive and reactive. "Proactive" feedback maintains basal activity of the hypothalamic-pituitary-adrenal axis, whereas the termination of stress-induced hypothalamic-pituitary-adrenal activity is facilitated by "reactive" feedback. In the present study we studied the ontogeny of both feedback modes and tested the hypothesis that the development of feedback depends on mother-pup interaction.

On postnatal day 9 or 12, pups were deprived (DEP) of the dam for 24 h; nondeprived pups of the same age served as controls. The pups were adrenalectomized (ADX) at the end of deprivation and given corticosterone (CORT) replacement by either injection or pellet implants using the following two designs: first at the time of adrenalectomy (ADX) to test the role of CORT in the maintenance of basal ACTH levels, and then 3 h after ADX, to investigate CORT suppression of elevated ACTH levels induced by prior ADX.

Regarding proactive feedback, the results showed that injection of CORT at the time of ADX was only partially effective in preventing ACTH elevations, whereas CORT pellets maintained basal levels of ACTH in all ADX pups. The reactive mode of negative feedback in nondeprived pups was resistant to CORT injection, whereas the CORT pellet resulted in a return to basal levels within 60 min. Maternal deprivation did not affect proactive feedback, but caused a more sustained increase in ACTH levels and a failure to return to basal levels 3 h after ADX despite significantly higher levels of circulating CORT in these DEP pups.

It is concluded that 1) proactive and reactive modes of negative feedback are operative, provided the pups are maintained on chronic replacement with CORT; 2) DEP impairs the reactive, rather than the proactive, mode of feedback inhibition in the neonate.

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