Olanzapine and progesterone have dose-dependent and additive effects to enhance lordosis and progestin concentrations of rats.

There is evidence that actions of both progesterone (P) and its metabolite, 5alpha-pregnane-3alpha-ol-20-one (3alpha,5alpha-THP), are important for sexual behavior of estradiol (E(2))-primed rodents. Olanzapine, an atypical antipsychotic, dose-dependently increases 3alpha,5alpha-THP in the cortex of male rats. These experiments investigated the effects of olanzapine administration on female sexual behavior and progestin concentrations. In Experiment 1, ovariectomized (ovx) rats (N=128) were primed with estradiol benzoate (EB) at Hour 0 and were administered P (0, 50, 100, or 200 microg sc) at Hour 44 and olanzapine (0.0, 2.5, 5.0, or 10.0 mg/kg ip) at Hour 47. At Hour 48, rats were tested for sexual receptivity with a stimulus male. Administration of 10.0 mg/kg of olanzapine, irrespective of P, significantly increased the occurrence (lordosis quotients, LQs) and the intensity (lordosis ratings, LRs) of lordosis compared to all other dosages. Administration of 2.5 or 5.0 mg/kg of olanzapine, irrespective of P, increased LQs and LRs compared to vehicle administration. Olanzapine without P dose-dependently increased LQs and LRs. As expected, administration of P without olanzapine also dose-dependently increased LQs and LRs. In Experiment 2, ovx rats (N=44, n=4 per group) received EB (0 or 10 microg sc), P (0 or 200 microg sc), and/or olanzapine (0.0, 2.5, 5.0, or 10.0 mg/kg ip). The same pattern of effects seen for lordosis was observed on progestin concentrations. Whole brain and plasma P and 3alpha,5alpha-THP concentrations were increased with olanzapine or P dosing and were greatest with coadministration. Together, these data demonstrate that olanzapine and P have independent effects to increase lordosis, P, and 3alpha,5alpha-THP concentrations of adult rats and additive effects in combination, suggesting complimentary mechanisms of action.