Wistar-Kyoto (WKY) rats provide a model of stress-induced depressive behavior, because they show enhanced vulnerability to the effects of stressors. The present study examined differences in the behavioral response to different types of antidepressant drugs between WKY and Sprague-Dawley (SD) rats in the forced swimming test (FST). WKY rats displayed significantly greater immobility than SD rats during their exposure to the FST. The noradrenergic antidepressant, desipramine, produced a dose-dependent reduction of immobility and increase of climbing behavior in the SD rats. In WKY rats, desipramine reduced immobility at a lower dose and produced increases of both swimming and climbing behavior. The serotonergic compounds, fluoxetine and 8-OH-DPAT, produced dose-dependent reductions of immobility and increases of swimming behavior in the FST in SD rats, but the response to the serotonergic drugs were blunted in WKY rats. These results indicate that genetic or constitutive differences may determine the distinct behavioral profiles for antidepressant compounds with selective pharmacological effects in different rat strains, and these effects may be related to genetic heterogeneity of antidepressant responses in depressed patients.