O. Picazo et A. Fernandezguasti, ANTI-ANXIETY EFFECTS OF PROGESTERONE AND SOME OF ITS REDUCED METABOLITES - AN EVALUATION USING THE BURYING BEHAVIOR TEST, Brain research, 680(1-2), 1995, pp. 135-141
In this study, pregnenolone sulfate, progesterone and some of its main
reduced metabolites were tested for anxiolytic properties in rats usi
ng the burying behavior paradigm. All steroids were subcutaneously inj
ected. Progesterone (0.5, 1.0, 2.0 and 4.0 mg/rat) and its 3 alpha-5 a
lpha-reduced metabolite (0.125, 0.250, 0.5 and 1.0 mg/rat) produced a
clear dose-dependent anxiolytic response, without affecting the sponta
neous ambulatory behavior. 5 alpha-Pregnanedione decreased burying beh
avior 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-preg
nanolones were devoid of effects. The 3 beta-5 beta-reduced metabolite
of progesterone (2.0 and 4.0 mg/rat) decreased motor activity, withou
t 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-acti
vity relationship requirements of steroids to stimulate the GABA/benzo
diazepine receptor-chloride ionophore complex.