National Library of Medicine: IGM
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TITLE:
Anxiolytic effect of progesterone is associated
with increases in cortical allopregnanolone and GABAA receptor function.
AUTHOR:
Bitran D; Purdy RH; Kellogg CK
AUTHOR AFFILIATION:
Department of Psychology, College of the Holy
Cross, Worcester, MA 01610.
SOURCE:
Pharmacol Biochem Behav 1993 Jun;45(2):423-8
NLM CIT. ID:
93317722
ABSTRACT:
The effects of a SC injection of progesterone (0,
1, or 4 mg) on locomotor behavior and exploration of an elevated plus-maze were examined
in ovariectomized rats. At the completion of the behavioral tests, blood serum and
cerebral cortical level of the 3 alpha-hydroxy ring-A metabolite of progesterone, 3
alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone), was also assessed.
GABA-stimulated 36Cl- influx was studied in cortical synaptoneurosomes from a subgroup of
ovariectomized females treated with vehicle or 4 mg progesterone. Whereas progesterone
treatment did not affect ambulation in a novel arena, significant anxiolytic behavior was
detected in the plus-maze 4 h after administration of 1 or 4 mg progesterone. A
dose-dependent increase in allopregnanolone level was found in serum and cortical
homogenates. Studies of GABA-stimulated Cl- influx demonstrated that progesterone
treatment increased the sensitivity of cortical synaptoneurosomes to GABA (i.e., decreased
the EC50) and increased the maximal efficacy with which GABA stimulated Cl- transport
(i.e., increased the Emax). Together, these data support the hypothesis that the
psychotropic effects observed after progesterone administration are due to the
bioconversion of progesterone to allopregnanolone, which subsequently augments GABAA
receptor-mediated function.
When my office
lease expired at the end of 2004, I decided to turn it into a
"sabbatical" from my private practice. Many years ago, in my
grandfather's 89th year of life, he told me, "John, it is important
to smell the roses while you can still smell them." His life
gave living a very good reputation. It is also true that the
pursuit of that philosophy required my grandfather to to re-open his
assay office/ore market in Wickenburg, Arizona as a 75-year-old because
he had run a little short of retirement money. Thus, if blessed with his
luck and health, I'll be back.. --jjh
