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, 5alpha-pregnane-3alpha-ol-20-one (3alpha,5alpha-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 (IP: 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, IP) significantly increased plasma and produced non-significant increases in whole brain concentrations of progesterone and 3alpha,5alpha-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. (C) 2003 Elsevier Science Ltd. All rights reserved.