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TITLE:
Anxiolytic effect of progesterone is mediated by
the neurosteroid allopregnanolone at brain GABAA receptors.
AUTHOR:
Bitran D; Shiekh M; McLeod M
AUTHOR AFFILIATION:
Department of Psychology, College of the Holy
Cross, Worcester, MA 01610, USA.
SOURCE:
J Neuroendocrinol 1995 Mar;7(3):171-7
NLM CIT. ID:
95330060
ABSTRACT:
Previous studies from this laboratory have shown
that progesterone (PROG) treatment in ovariectomized rats produces an anti-anxiety
response similar to that observed after the administration of prototypical anxiolytic
benzodiazepine (BDZ) compounds. The PROG-induced anxiolytic response was highly correlated
with an increased level of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) in
the blood and brain, and was also associated with a facilitation of GABA-stimulated
chloride ion (Cl-) influx in cortical synaptoneurosomes. This correlative evidence
suggested that the anxiolytic effect of PROG was a result of its in vivo reduction to the
neuroactive steroid, allopregnanolone. In this report, a series of studies was conducted
to determine the mechanism(s) by which PROG alters behavior in animal models of anxiety.
In the first experiment, ovariectomized rats were injected with PROG (1 mg/0.2 ml, SC) 4 h
prior to a test in the elevated plus-maze. Some animals also received an injection of
picrotoxin (0.75 mg/kg, IP), a GABAA receptor-gated Cl- channel antagonist, whereas other
animals were pretreated with RU 38486 (5 mg/0.2 ml, SC), a progestin receptor antagonist.
PROG elicited anxiolytic behavior in the plus-maze, an effect that was blocked by
picrotoxin administration. Pretreatment with RU 38486 was not effective in altering
PROG-induced anxiolytic behavior in the plus-maze. In a second experiment, the effect of
PROG on behavior in the plus-maze was determined in the presence of
N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA; 10 mg/0.2
ml, SC), a 5 alpha-reductase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
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
