Behavioral effects of acute and chronic fluoxetine in Wistar-Kyoto rats.

It has been previously reported that Wistar-Kyoto (WKY) rats may be useful in the study of the biological mechanisms involved in stress-related disorders. In the present study, WKY were treated acutely or chronically (one daily i.p. injection for 22-24 days) with the selective 5-HT reuptake inhibitor and clinically effective antidepressant and anxiolytic fluoxetine (5 and 20 mg/kg) and exposed to the forced swimming test (FST) and to the elevated plus-maze (EPM) at different times postinjection (30, 60, min or 24 h). In the FST, WKY failed to respond to fluoxetine, regardless of treatment. In the EPM, acute fluoxetine (20 mg/kg) produced anxiolytic-like effects when animals were tested 24 h, but not 30 min after drug administration. Positive effects in the EPM were evident on both conventional (open-arm activity) and ethological (risk assessment) measures in the absence of effect on activity measures (total and closed-arm entries). No evidence for anxiolytic-like activity was observed following chronic fluoxetine. These results indicate that WKY rats are resistant to fluoxetine treatment in the FST, while their behavior may be modified in the EPM when animals received a single fluoxetine challenge 24 h before testing. Overall, these findings provided little evidence that WKY rats may represent a valid model of stress-related disorders.