Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats

In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17 beta-estradiol (E-2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E-2 (5, 10, 20 and 40 mu g/rat) or the combination of E-2 [at sub-threshold (5 mu g/rat) and optimal (10 mu g/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E-2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E-2 at the supra-physiological doses of 10 and 20 mu g/rat produced antidepressant-like effects. E-2 at 5 mu g/rat (that re-established the levels of this hormone to physiological levels) and at 10 mu g/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST. (C) 2007 Elsevier Inc. All rights reserved.