National Library of Medicine: IGM
Full Record Screen
TITLE:
Behaviorally selective effects of neuroactive
steroids on plus-maze anxiety in mice.
AUTHOR:
Rodgers RJ; Johnson NJ
AUTHOR AFFILIATION:
Ethopharmacology Laboratory, School of
Psychology, University of Leeds, UK.
SOURCE:
Pharmacol Biochem Behav 1998 Jan;59(1):221-32
NLM CIT. ID:
98103796
ABSTRACT:
A number of A-ring-reduced metabolites of
deoxycorticosterone and progesterone, known to exert agonist activity at the GABA(A)
receptor complex, have been reported to reduce anxiety-related behavior in rodents. In the
present study, the behavioral selectivity of these effects was assessed in an ethological
version of the mouse elevated plus-maze paradigm. Anxiolytic-like profiles, characterised
principally by reductions in open arm avoidance measures, were observed following systemic
treatment with 5alpha-pregnan-3alpha, 21-diol-20-one (5alpha,3alpha-THDOC; 5.0 and 20.0
mg/kg), 5beta-pregnan-3,20-dione (5beta-DHP; 10-20 mg/kg), 5beta-pregnan-3alpha-ol-20-one
(pregnanolone; 20 mg/kg), and 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone; 10-20
mg/kg). In contrast, 5alpha-pregnan-3,20-dione (5alpha-DHP; 10.0-20.0 mg/kg) and
5alpha-pregnan-3beta-ol-20-one (2.5-20.0 mg/kg) were without effect under present test
conditions. Detailed behavioral analysis further showed that the antianxiety effects of
5alpha,3alpha-THDOC, 5alpha-DHP, pregnanolone and allopregnanolone were not associated
with changes in general activity levels. In addition, profile comparisons revealed that
the anxiolytic steroids tend to produce a narrower range of behavioral effects than
diazepam (1.0 mg/kg) and, in particular, do not reliably decrease measures of risk
assessment. It is concluded that neuroactive steroids produce anxioselective effects in
the mouse plus-maze and that their profile of action can at least partially be
distinguished from that of a well-characterised benzodiazepine.
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
