TY - JOUR
T1 - Anti-anxiety effects of progesterone and some of its reduced metabolites
T2 - an evaluation using the burying behavior test
AU - Picazo, O.
AU - Ferna ́ndez-Guasti, A.
N1 - Funding Information:
This work was supported by a grant from the 'Con-sejo Nacional de Ciencia y Teconologia' (1709-M9209). The authors wish to thank Dr. Rodriguez-Manzo for language checking, Mr. Facundo Moreno for technical assistance, and Victor Flores for animal care. O.P. received a doctorate fellowship from the 'Consejo Na-cional de Ciencia y Tecnologla'
PY - 1995/5/22
Y1 - 1995/5/22
N2 - 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 3α-5α-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. 5α-Pregnanedione decreased burying behavior only at the highest dose (4.0 mg/rat). Pregnenolone sulfate (1.0, 2.0 and 4.0 mg/rat), 5β-pregnanedione and 3β or 5β-pregnanolones were devoid of effects. The 3β-5β-reduced metabolite of progesterone (2.0 and 4.0 mg/rat) decreased motor activity, without altering the burying behavior. These results demonstrate that the 3α-5α 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.
AB - 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 3α-5α-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. 5α-Pregnanedione decreased burying behavior only at the highest dose (4.0 mg/rat). Pregnenolone sulfate (1.0, 2.0 and 4.0 mg/rat), 5β-pregnanedione and 3β or 5β-pregnanolones were devoid of effects. The 3β-5β-reduced metabolite of progesterone (2.0 and 4.0 mg/rat) decreased motor activity, without altering the burying behavior. These results demonstrate that the 3α-5α 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.
KW - 3α-Hydroxy-5α-pregnan-20-one
KW - Anxiety
KW - Burying behavior
KW - Motor activity
KW - Progesterone
KW - Rat
KW - Steroid
UR - http://www.scopus.com/inward/record.url?scp=0029056668&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(95)00254-N
DO - 10.1016/0006-8993(95)00254-N
M3 - Artículo
SN - 0006-8993
VL - 680
SP - 135
EP - 141
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -