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Vol. 282, Issue 3, 1213-1218, 1997
Max Planck Institute of Psychiatry, Clinical Institute, Munich,
Germany (M.L., J.F., T.S., F.H., R.R.), and
Universita' Tor Vergata,
Dipartimento di Medicina Sperimentale, Rome, Italy (E.R., F. di M.)
Recent research in rats and humans has shown that exogenous
progesterone evokes a sleep profile similar to that induced by agonistic modulators of 
-aminobutyric acidA
receptors, such as benzodiazepines. This finding suggests the
involvement of the neuroactive metabolite of progesterone,
allopregnanolone. In the vehicle-controlled study reported here, we
assessed the sleep effects of two doses of allopregnanolone (7.5 and 15 mg/kg), mixed with oil, administered intraperitoneally at light onset
in 8 rats. The electroencephalogram (EEG) and electromyogram were
recorded during the first 6 postinjection hr. Compared with vehicle,
both doses of allopregnanolone reduced the latency to non-rapid eye movement sleep (non-REMS) and 15 mg/kg allopregnanolone significantly increased the time spent in pre-REMS, an intermediate state between non-REMS and REMS. Furthermore, allopregnanolone dose-dependently influenced EEG activity during non-REMS and REMS. In non-REMS, EEG
activity was decreased in the lower frequencies (
7 Hz) and enhanced
in the frequencies of 
13 Hz. In REMS, allopregnanolone enhanced
high-frequency EEG activity (17 Hz). The effects were most pronounced
during the first postinjection hours and gradually diminished
thereafter. Analysis of the plasma and brain concentrations of
allopregnanolone in 45 rats revealed long-lasting increases, which
reached maximal levels during the first postinjection hour. The sleep
effects of allopregnanolone are very similar to those elicited by
larger doses of progesterone, which produce comparable brain levels of
allopregnanolone. These data indicate that the steroid allopregnanolone
has benzodiazepine-like effects on sleep.
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