Olanzapine plus 17-β estradiol produce antidepressant-like actions in rats forced to swim

Several combinations of effective treatments have been used in the search for higher response rates or more rapid responses than monotherapy to diminish treatment-resistant depression. One strategy is to combine olanzapine plus antidepressant drugs. In preclinical studies in male rats, olanzapine combined with fluoxetine produce antidepressant-like actions and increase the allopregnanolone levels in the brain. 17-β estradiol also produces antidepressant-like actions by increasing allopregnanolone levels. However, the effects of combining olanzapine with 17-β estradiol in the forced swimming test have not been tested before. Thus, systemic injections of vehicle plus olanzapine, or fluoxetine (20.0 mg/kg; 25.0 mg/kg) or 17-β estradiol (10.0 μg/rat; 20.0 μg/rat) reduced immobility by increasing active behaviors, which were cancelled by finasteride (finasteride was used to block the endogenous production of allopregnanolone by the brain) in ovariectomized rats forced to swim. Subthreshold doses of olanzapine (2.5 mg/kg) combined with subthreshold doses of 17-β estradiol (5.0 μg/rat) produced antidepressant-like actions, as did the combination subthreshold dose of olanzapine (2.5 mg/kg) plus the subthreshold dose of fluoxetine (15.0 mg/kg). Finasteride cancelled the antidepressant-like actions of the several combinations used. It is concluded that olanzapine alone or combined with fluoxetine or estradiol reduced immobility by increasing swimming. In conclusion, olanzapine produces antidepressant-like actions alone or in combination with estradiol. These antidepressant-like actions of this combination were cancelled by finasteride.