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Objective Depression is a severe illness and the prevalence increased gradually in the past decades according to large epidemiological studies.So, it is crucial to prevent the onset of the disease and approach effective treatment.The aim of the present study was to examine whether Escitalopram treatment can cause antidepressant-like effect and behavior changes in helpless rats, rat models of depression.Methods 76 male SD rats were randomly divided into 5 groups: normal (n =11), model (n =11), depression + Saline (n =10), depression + Escitalopram (n =8), and depression + Clomipramine (as positive control, n =11).On 2 consecutive days, rats were exposed to 60 inescapable electric foot-shocks (IS).Escape-avoidance behavior was evaluated 3 days after IS.Animals that failed to escape between 10 and 30 trials were considered "helpless".Then Escitalopram and Clomipramine treatments were given to helpless rats twice daily (intraperitoneal injection) at the dose of 10 mg/kg for 5 d starting on the evening of the third day after IS.After medication, the escape-avoidance behavior was evaluated again.Other depressive-like behaviors were evaluated before IS, after IS and treatment with drug in forced swimming and open field test through the paradigm.Results As for the number of escape failures in the active avoidance task, the one-way ANOVA indicated a significant effect of treatment with escitalopram (F =69.28, P < 0.01).After inescapable footshoek, helpless rats displayed significantly increased escape failure times.As expected, helpless rats treated with escitalopram and clomipramine displayed decreased number of escape failures, as compared with helpless rats (F =17.05, P < 0.01).The open field test is a test of spontaneous motor activity for rats.After inescapable shook, the total distance of travel (F =29.36, P < 0.01) of helpless rats was significantly decreased in the OFT.After escitalopram and clomipramine treatment, the total distance of travel (F =8.79, P < 0.01) of medication-treated rats significantly increased compared with the helpless rats.The force swimming test can indicate despair reaction of the helpless rats.After inescapable shook, the struggling time (F =35.77, P < 0.01) of helpless rats was significantly decreased after inescapable shook in the FST.As expected, the struggling time (F =78.54, P < 0.01) of medication-treated rats significantly increased compared with the helpless rats.Conclusion The behavioral changes of helpless rats after escitalopram treatment are similar as clomipramine treatment.The escape-avoidance behavior, spontaneous motor activity and despair behavior of helpless rats can be improved after escitalopram or clomipramine treatment.