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Pharmacol Biochem Behav. 1993 Jun;45(2):423-8.

Anxiolytic effect of progesterone is associated with increases in cortical allopregnanolone and GABAA receptor function.

Author information

1
Department of Psychology, College of the Holy Cross, Worcester, MA 01610.

Abstract

The effects of a SC injection of progesterone (0, 1, or 4 mg) on locomotor behavior and exploration of an elevated plus-maze were examined in ovariectomized rats. At the completion of the behavioral tests, blood serum and cerebral cortical level of the 3 alpha-hydroxy ring-A metabolite of progesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone), was also assessed. GABA-stimulated 36Cl- influx was studied in cortical synaptoneurosomes from a subgroup of ovariectomized females treated with vehicle or 4 mg progesterone. Whereas progesterone treatment did not affect ambulation in a novel arena, significant anxiolytic behavior was detected in the plus-maze 4 h after administration of 1 or 4 mg progesterone. A dose-dependent increase in allopregnanolone level was found in serum and cortical homogenates. Studies of GABA-stimulated Cl- influx demonstrated that progesterone treatment increased the sensitivity of cortical synaptoneurosomes to GABA (i.e., decreased the EC50) and increased the maximal efficacy with which GABA stimulated Cl- transport (i.e., increased the Emax). Together, these data support the hypothesis that the psychotropic effects observed after progesterone administration are due to the bioconversion of progesterone to allopregnanolone, which subsequently augments GABAA receptor-mediated function.

PMID:
8392205
[Indexed for MEDLINE]

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