Objective To investigate the effects of fluoxctine and amitriptyline on rat behaviors in the forced swimming test(FST)and phosphoryhted ERK1/2 level in the rat brain.Methods Thirty male SD rats were randomly divided into three groups(n=10):ftuoxefine(FLX),amitriptyline(AMT) and control(CON) groups.Treated groups were injected with 20 mg/kg fluoxetine and 20 mg/kgamitriptyline,respectively,23 h after the 15-rain pie-test of FST.The animals in CON group were injected with the same volume of distilled water.Thell a 5-min FST was conducted 1 h later.The 5-min test sessions were videotaped and the time span for each behavior(latency of immobility.immobility,swimming and climbing)was recorded.All rats were sacrificed with a perfusion of 4% paraformaldehyde immediately after the termination of the test.Immunohistochernical ABC staining was used to observe the distribution of pERK1/2-like immunoreactive(LI)neurons in the brain. Results(1)The latency of immobility in AMT group was significantly longer than that of CON group during the 5 min FST (P<0.05),and the climbing time in AMT group was longer than that of CON group and FLX group(P<0.05),while the duration of immobility in AMT group was obviously shorter in comparison with CON group (P<0.05).The duration of swimming behavior in FLX group was longer than that of CON group as well as AMT group(p<0.05).(2)Numbers of pERK1/2-LIneurons in FLX group were greatly reduced in prefrontal codex(PFC),cingulate gyms(Cg)and prelimbic cortex(Prl) in comparison with that of CON and AMT group(P<0.05),while the expressed pERK1/2 in AMT group was significantly decreased in the neurons of ventrolateral septum(LSV)in comparison with that of CON group(P<0.05).And compared with CON group,the numbers of pERKl/2-LI neurons in both drug treated groups were greatly reduced in hypothalamic paraventricular nucleus (PVN) and more significantly in AMT group(P<0.01).Conclusion Administration of fluoxetine and amitriptyline have different effects on rat behaviorals in the FST.Both of them may be have some effects on anti-negative psychological stress.The ERKI/2 pathway possibly plays a role in this process.