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Vol. 95, Issue 22, 13284-13289, October 27, 1998
* Department of Experimental Biology, University of Cagliari, 09123 Cagliari, Italy; Communicated by Erminio Costa, University of Illinois, Chicago, IL, August 14, 1998 (received for review November 4, 1997)
The relation between changes in brain and plasma concentrations of
neurosteroids and the function and structure of
Copyright © 1998 by The National Academy of Sciences 0027-8424/98/9513284-6$2.00/0
Neurobiology
Role of brain allopregnanolone in the plasticity of
-aminobutyric acid type A receptor in rat brain during pregnancy and
after delivery
,
,, Department of Neuroscience, University of
Rome Tor Vergata, 00133 Rome, Italy; § Department of Psychiatry,
University of California, San Diego, CA 92161; and ¶ Poli
Industria Chimica, Quinto de Stampi, 20089 Rozzano (MI), Italy
-aminobutyric acid
type A (GABAA) receptors in the brain during pregnancy and after delivery was investigated in rats. In contrast with plasma, where
all steroids increased in parallel, the kinetics of changes in the
cerebrocortical concentrations of progesterone, allopregnanolone (AP),
and allotetrahydrodeoxycorticosterone (THDOC) diverged during pregnancy. Progesterone was already maximally increased between days 10 and 15, whereas AP and allotetrahydrodeoxycorticosterone peaked around
day 19. The stimulatory effect of muscimol on
36Cl
uptake by cerebrocortical membrane
vesicles was decreased on days 15 and 19 of pregnancy and increased 2 days after delivery. Moreover, the expression in cerebral cortex and
hippocampus of the mRNA encoding for 2L GABAA receptor
subunit decreased during pregnancy and had returned to control values 2 days after delivery. Also 
1,2, 3, 4, 
1, 2, 3, and
2S mRNAs were measured and failed to change during pregnancy.
Subchronic administration of finasteride, a 5-reductase inhibitor,
to pregnant rats reduced the concentrations of AP more in brain than in
plasma as well as prevented the decreases in both the stimulatory
effect of muscimol on 36Cl uptake and the
decrease of 2L mRNA observed during pregnancy. These results
indicate that the plasticity of GABAA receptors during
pregnancy and after delivery is functionally related to fluctuations in
endogenous brain concentrations of AP whose rate of
synthesis/metabolism appears to differ in the brain, compared with
plasma, in pregnant rats.
To whom reprint requests should be addressed. e-mail:
aconcas{at}vaxca1.unica.it.
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