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 disord ers. In the present study, WKY were treated acutely or chronically (one dai ly i.p. injection for 22-24 days) with the selective 5-HT reuptake inhibito r 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. Positi ve effects in the EPM were evident on both conventional (open-arm activity) and ethological (risk assessment) measures in the absence of effect on act ivity measures (total and closed-arm entries). No evidence for anxiolytic-l ike activity was observed following chronic fluoxetine. These results indic ate that WKY rats are resistant to fluoxetine treatment in the FST, while t heir behavior may be modified in the EPM when animals received a single flu oxetine challenge 24 h before testing. Overall, these findings provided lit tle evidence that WKY rats may represent a valid model of stress-related di sorders. (C) 1999 Elsevier Science Inc.