Hormones and behavior
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Hormones and behavior · Mar 1996
Allopregnanolone (THP) mediates anesthetic effects of progesterone in rat brain.
Intravenous infusion of the progesterone or that of progesterone 5 alpha-reduced metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (THP), induces the loss of righting reflex in freely moving rats at the doses of 49 +/- 15 mg/kg or 5.6 +/- 2.2 mg/kg, respectively. The recovery time of righting reflex was 71 +/- 12 min and 21 +/- 5 min for progesterone and THP, respectively. The time course of brain concentrations of THP, but not that of progesterone, correlated with the loss and the recovery of righting reflex. ⋯ Following progesterone infusion brain level of THP in SKF 105111 pretreated rats was 12% that of vehicle-treated control, and the level of progesterone was 160%. No effect of SKF 105111 on brain THP level was detected in animals infused with THP. These results demonstrate that anesthetic effect of progesterone is mediated through its conversion to THP and support the hypothesis that endogenous metabolites of progesterone may be involved in the regulation of behavior in rats.