Testosterone-dependent antidepressant-like effect of noradrenergic but not of serotonergic drugs.

The main objective of this study was to analyze the effect of testosterone on the actions of antidepressant drugs in the forced swimming test (FST), an animal model that predicts antidepressant effects. In addition, the effect of testosterone propionate (TP) supplementation was evaluated in the same animal model using orchidectomized male rats. Initially, different doses (2.5, 5.0, and 10.0 mg/kg sc, three injections before the test) of desipramine (DMI), fluoxetine (FLX), and clomipramine (CMI) were administered to intact male rats to detect the effective dose in the FST. All drugs (at 10 mg/kg) produced an antidepressant effect, reflected as a reduction of immobility behavior. Neither orchidectomy per se nor TP supplementation (0.5 and 1.0 mg/rat sc, for 10 days) modified the behaviors evaluated in the FST. Orchidectomy blocked the antidepressant effect of DMI, FLX, and CMI (10 mg/kg), while TP supplementation (0.5 mg/rat, for 10 days) restored the antidepressant action of DMI, but not that of CMI or FLX. These findings indicate that testosterone participates in the antidepressant actions of DMI, a noradrenaline reuptake inhibitor, while other gonadal hormones might be involved in the antidepressant effects of the serotonin reuptake inhibitors (SSRIs) like FLX and CMI. Copyright 2004 Elsevier Inc.