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Publication : Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase Type 1 mutant, mice.

First Author  Koonce CJ Year  2013
Journal  Behav Brain Res Volume  253
Pages  232-9 PubMed ID  23886595
Mgi Jnum  J:202105 Mgi Id  MGI:5517497
Doi  10.1016/j.bbr.2013.07.025 Citation  Koonce CJ, et al. (2013) Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5alpha-reductase Type 1 mutant, mice. Behav Brain Res 253:232-9
abstractText  Progesterone (P4) facilitates exploration, anxiety and social behaviors in estrogen (E2)-primed mice. Some of these effects may be due to actions of its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). In order to address the role of P4 and its metabolite, 3alpha,5alpha-THP, a mouse model was utilized. We hypothesized that if P4's metabolism to 3alpha,5alpha-THP is essential to facilitate exploratory, anti-anxiety and social behaviors of mice, then wildtype, but not 5alpha-reductase knockout (5alpha-RKO), mice will have greater expression of these behaviors. Experiment 1: Mice were ovariectomized (ovx), E2-primed and administered P4 (0, 125, 250, or 500mug) subcutaneously and then tested 4h later in a battery of tasks: open field, elevated plus maze, and social interaction. Experiment 2: Ovx, E2-primed mice were administered P4 (4mg/kg), 3alpha,5alpha-THP (4mg/kg), medroxyprogesterone acetate (MPA, which does not convert to 3alpha,5alpha-THP; 4mg/kg), or vehicle subcutaneously and tested 4h later. There was a dose-dependent effect of P4 to wildtype, but not 5alpha-RKO, mice. Neither wildtype, nor 5alpha-RKO, mice had increased exploration, anti-anxiety or pro-social behavior with MPA administration. Progesterone only exerted effects on anti-anxiety behavior, and increased 3alpha,5alpha-THP in the prefrontal cortex and hippocampus, when administered to wildtype mice. 3alpha,5alpha-THP to both WT and 5alpha-RKO mice increased exploration, anti-anxiety and social interaction and 3alpha,5alpha-THP levels in the hippocampus and prefrontal cortex. Thus, metabolism of P4 by the 5alpha-reductase enzyme may be essential for enhancement of these behaviors.
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