Progesterone induces changes in sleep comparable to those of
agonistic gabaa receptor modulators.
Lancel, Marike, Johannes Faulhaber, Florian Holsboer, and Rainer
Rupprecht.
Max Planck Institute of Psychiatry, Clinical Institute, Munich,
Germany
APStracts 3:0165E, 1996.
There is much evidence that progesterone (P) has hypnotic-anesthetic
properties. In this vehicle-controlled study we examined the effects
of three doses of P (30, 90 and 180 mg/kg) administered
intraperitoneally at light onset on sleep in rats. P dose-dependently
shortened non-rapid-eye-movement sleep (nonREMS) latency, lengthened
REMS latency, decreased the amount of wakefulness and REMS and
markedly increased preREMS, an intermediate state between nonREMS and
REMS. P also elicited dose-related changes in sleep state-specific
EEG power densities. Within nonREMS, EEG activity was reduced in the
lower frequencies ( 7 Hz) and enhanced in the higher frequencies.
Within REMS, EEG activity was markedly enhanced in the higher
frequencies. The effects were maximal during the first post injection
hours. The concentrations of P and the P-metabolites 3a-hydroxy-5a
-pregnan-20-one and 3a-hydroxy-5b-pregnan-20-one, both positive
allosteric modulators of GABAA receptors, were determined at
different time intervals following vehicle, 30 or 90 mg/kg of P. P
administration resulted in dose-dependent, initially
supraphysiological elevations of P and its metabolites in the plasma
and brain, which were most prominent during the first post injection
hour. The effects of P on sleep closely resemble those of agonistic
modulators of GABAA receptors such as benzodiazepines and correlate
well with the increases in the levels of its GABAA-agonistic
metabolites. These observations suggest that the hypnotic effects of
P are mediated by the facilitating action of its neuroactive
metabolites on GABAA receptor functioning.
Received 8 May 1996; accepted in final form 12 July 1996.
APS Manuscript Number E226-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996