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 Previous Article
Volume 16, Number 17,
Issue of September 1, 1996
pp. 5555-5565
Copyright ©1996 Society for Neuroscience
A Diurnal Rhythm of Stimulatory Input to the
Hypothalamo-Pituitary-Adrenal System as Revealed by Timed
Intrahypothalamic Administration of the Vasopressin V1
Antagonist
Received Jan. 31, 1996; revised June 10, 1996; accepted June 13, 1996.
Andries Kalsbeek,
Joop J. van
Heerikhuize,
Joke Wortel, and
Ruud
M. Buijs
Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The
Netherlands
The mammalian suprachiasmatic nuclei (SCN) contain an endogenous
pacemaker that generates daily rhythms in behavior and secretion of
hormones. We hypothesized that the SCN imposes its circadian rhythm on
the rest of the brain via a rhythmic release of its transmitters in its
target areas. Previously, we demonstrated a pronounced inhibitory
effect of vasopressin (VP), released from SCN terminals in the
dorsomedial hypothalamus, on the release of the adrenal hormone
corticosterone. In the present study, microdialysis-mediated
intracerebral administration of the VP V1-receptor
antagonist was used to pursue the study of the mechanisms underlying
the circadian control of basal corticosterone release. Using timed
administrations of the VP antagonist divided equally over the day/night
cycle, we were able to uncover the existence of an additional
stimulatory input from the SCN to the hypothalamo-pituitary-adrenal
(HPA) axis. Peak activity of this stimulatory SCN input takes place
during the second half of the light period, after the daily peak of VP
secretion, with a delay of ~4-6 hr. In all likelihood, the
inhibitory and stimulatory circadian input via separate mechanisms
affects corticosterone release. Together, these two opposing circadian
control mechanisms of the HPA axis enable a precise timing of the
circadian peak in corticosterone release.
Key words:
circadian rhythms;
vasopressin;
glucocorticoids;
microdialysis;
paraventricular/dorsomedial hypothalamus;
suprachiasmatic nuclei
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