ANTI-ANXIETY EFFECTS OF PROGESTERONE AND SOME OF ITS REDUCED METABOLITES - AN EVALUATION USING THE BURYING BEHAVIOR TEST

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.