A-ring reduced derivatives of two synthetic progestins induce anxiolytic effects in ovariectomized rats

The putative anxiolytic action of the synthetic progestins, norethisterone (NET), levonorgestrel (LNG) and their respective 5 alpha-reduced metabolites, (5 alpha-NET), (3 alpha,5 alpha-NET), (3 beta,5 alpha-NET), (5 alpha-LNG), (3 alpha,5 alpha-LNG) and (3 beta,5 alpha-LNG), were studied in the burying behavior paradigm. From these compounds only 3 alpha,5 alpha-NET and 3 beta,5 alpha-LNG reduced burying behavior without modifying other parameters. Burying behavior latency was prolonged after administration of the highest dose (1.0 mg/rat) of NET and 5 alpha-NET. As a positive control 3 alpha,5 alpha-pregnanolone (allopregnanolone) was included at the same doses used for synthetic steroids. This steroid produced a clear dose-dependent reduction in burying behavior without affecting latency. No steroid with anxiolytic properties affected the general ambulatory behavior. All synthetic steroids with anxiolytic activity proved to be less potent than allopregnanolone. Results are discussed on the basis of the chemical structure requirements necessary to induce tranquilizing effects.