5alpha-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats.

Androgens may improve cognitive performance; however, these effects and mechanisms of androgens are not well understood. Whether testosterone's (T) effects on cognitive performance are mediated by its 5alpha-reduced, non-aromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha-androstanediol (3alpha-diol), was investigated. In Experiment 1, male rats that were gonadally intact, or gonadectomized (GDX) and DHT-replaced with a silastic capsule, had better performance in the inhibitory avoidance task, and higher plasma DHT and 3alpha-diol levels, compared to GDX rats. In Experiments 2-4, intra-hippocampal indomethacin, a 3alpha-HSD inhibitor, to intact or DHT-replaced, but not GDX, rats decreased performance in the inhibitory avoidance task and reduced hippocampal 3alpha-diol levels compared to that observed in rats with control implants. Thus, the 5alpha-reduced androgen DHT has cognitive-enhancing effects, independent of E(2), which are attenuated by a 3alpha-HSD inhibitor, indomethacin. These results suggest that 5alpha-reduced androgens may have actions in the hippocampus to improve cognitive performance.

Olanzapine's effects to reduce fear and anxiety and enhance social interactions coincide with increased progestin concentrations of ovariectomized rats.

Administration of olanzapine, an antipsychotic drug, can dose-dependently increase the levels of progesterone's metabolite, 5 alpha-pregnane-3 alpha-ol-20-one (3 alpha,5 alpha-THP) in the brain, which may have anxiolytic effects. The purpose of this experiment was to investigate the effects of olanzapine administration on anxiety behavior and progestin levels. Ovariectomized (ovx) rats (N=33) were administered olanzapine (i.p.: 5.0 or 10.0 mg/kg) or vehicle (saline buffered with acetic acid) and an hour later were tested for motor and anxiety behavior (n=8 per group) or had tissue collected for measurement of progestin concentrations (n=3 per group). Rats that were administered 5.0 or 10.0 mg/kg of olanzapine spent less time freezing in response to shock in the defensive burying task, spent more time on the open arms of the elevated plus-maze, and spent more time in social interaction with a conspecific than did vehicle-administered rats. Olanzapine (5.0 or 10.0 mg/kg, i.p.) significantly increased plasma and produced non-significant increases in whole brain concentrations of progesterone and 3 alpha,5 alpha-THP compared to that seen following vehicle administration. Together, these data are consistent with the hypothesis that olanzapine reduces fear, has anxiolytic effects, and may enhance social interaction in part due to increasing progestin concentrations.