The folic acid combined with 17-β estradiol produces antidepressant-like actions in ovariectomized rats forced to swim

Folic acid or 17-beta estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-beta estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0 nmol/i.c.v., P<0.05; 10.0 nmol/i.c.v., P<0.05; or 50 mg/kg, P<0.05, p.o.; 75.0; mg/kg, P<0.05, p.o.), or fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) or 17-beta estradiol (10.0 mu g/rat, P<0.05; 20.0 mu g/rat, P<0.05) and they displayed reduced immobility by increasing swimming behavior when they were tested in the FST. Combination of subthreshold doses of folic acid (2.5 nmol/i.c.v.; or 25.0 mg/kg, p.o.) with subthreshold doses of 17-beta estradiol (5.0 mu g/rat, P<0.05) or with subthreshold doses of fluoxetine (15.0 mg/kg, P<0.05) produced antidepressant-like actions. Ketanserin was used to evaluate the participation of the drugs used in the serotonergic pathway; ketanserin cancelled the antidepressant-like actions of the several combinations used. In conclusion, folic acid alone or combined with estradiol or fluoxetine in the FST reduced immobility in the FST. These antidepressant-like actions probably were due to modifications of the serotonergic system since swimming behavior was increased and these effects were cancelled by ketanserin. (C) 2010 Elsevier Inc. All rights reserved.