Abstract Title:

Anesthetic effects of progesterone are undiminished in progesterone receptor knockout mice.

Abstract Source:

Brain Res. 2005 Feb 1;1033(1):96-101. PMID: 15680344

Abstract Author(s):

Doodipala S Reddy, Leigh Ann Apanites

Article Affiliation:

Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA. [email protected]


Progesterone has sedative and anesthetic effects but the underlying molecular mechanisms remain unclear. The two possible mechanisms by which progesterone affects the function of the brain include binding to intracellular progesterone receptors (PR) and metabolism to GABA(A) receptor-modulating neurosteroids. In this study, PR knockout (PRKO) mice were used as model to study the role of PRs in the anesthetic activity of progesterone. The progesterone-induced anesthetic activity was undiminished in female PRKO mice (ED50, 172 mg/kg) as compared to their wild-type littermates (ED50, 167 mg/kg). The progesterone-induced anesthetic activity was highly correlated with increased plasma allopregnanolone levels. Pretreatment of PRKO mice with the 5alpha-reductase inhibitor finasteride significantly reduced the progesterone-induced anesthetic activity. Allopregnanolone also evoked dose-dependent anesthetic activity in PRKO mice, which was similar to those of wild-type mice. Thus, the anesthetic activity of progesterone is not mediated by its interaction with PRs. The neurosteroid allopregnanolone partially mediates the anesthetic activity of progesterone by potentiation of GABA(A) receptor function.

Study Type : Animal Study

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