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Anti-anxiety effects of progesterone and some of
its reduced metabolites: an evaluation using the burying behavior test.
Picazo O; Fernandez-Guasti A
Departamento de Farmacologia y Toxicologia,
CINVESTAV, Mexico, D.F., Mexico.
Brain Res 1995 May 22;680(1-2):135-41
NLM CIT. ID:
In this study, pregnenolone sulfate, progesterone
and some of its main reduced metabolites were tested for anxiolytic properties in rats
using the burying behavior paradigm. All steroids were subcutaneously injected.
Progesterone (0.5, 1.0, 2.0 and 4.0 mg/rat) and its 3 alpha-5 alpha-reduced metabolite
(0.125, 0.250, 0.5 and 1.0 mg/rat) produced a clear dose-dependent anxiolytic response,
without affecting the spontaneous ambulatory behavior. 5 alpha-Pregnanedione decreased
burying behavior only at the highest dose (4.0 mg/rat). Pregnenolone sulfate (1.0, 2.0 and
4.0 mg/rat), 5 beta-pregnanedione and 3 beta- or 5 beta-pregnenolones were devoid of
effects. The 3 beta-5 beta-reduced metabolite of progesterone (2.0 and 4.0 mg/rat)
decreased motor activity, without altering the burying behavior. These results demonstrate
that the 3 alpha-5 alpha metabolite of progesterone shows the highest anxiolytic potency
in the burying behavior test, when compared with all steroids evaluated. The data are
discussed in terms of the close structure-activity relationship requirements of steroids
to stimulate the GABA/benzodiazepine receptor-chloride ionophore complex.
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