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

doi:10.1016/0091-3057(93)90260-Z

Pharmacology Biochemistry and Behavior

Volume 45, Issue 2, June 1993, Pages 423-428

https://doi.org/10.1016/0091-3057(93)90260-Z Get rights and content

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, blood serum and cerebral cortical level of the 3α-hydroxy ring-A metabolite of progesterone, 3α-hydroxy-5α-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 E_max). 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 GABA_A receptor-mediated function.

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

Abstract

Eur. J. Pharmacol.

Neurosci. Biobehav. Rev.

Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Meth. Enzymol.

Brain Res.

J. Neurosci. Meth.

J. Biol. Chem.

Neuron

Steroids

Psychoneuroendocrinology

Trends Neurosci.

Brain Res. Bull.

Brain Res.

Brain Res.

Ovarian endocrine status modulates the anxiolytic potency of diazepam and the efficacy of GABA/benzodiazepine receptor-mediated chloride ion transport

Behav. Neurosci.

Effects of single oral doses of bromazepam, buspirone, and clobazam on performance tasks and memory

Neuropsychobiology

Anxiolytic activity of an endogenous adrenal steroid

Brain Res.

A placebo-controlled study of effects of oral progesterone on performance and mood

Br. J. Clin. Pharmacol.

Anxiolytic effect of progesterone is associated with increases in cortical alloprenanolone and GABA_A receptor function