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Background & Aims: Type 2 diabetes (T2D) is a self-management disease and depression is a common problem related to it. One of the causes of depression is serotonin (5-HT) depleted. The enzyme tryptophan hydroxylase (TPH) is known as limiting enzyme in the production of 5-HT in the brain. Aerobic exercise also has proven benefits in treating and reducing the incidence of chronic diseases such as diabetes. Thus, in this study, we examine the effect of aerobic training on 5-HT and TPHof prefrontal cortex in type 2 diabetic rats. Materials & Methods: This study is experimental and post-test. 30 rats were randomly divided into 3 groups: 1healthy control 2diabetic control and 3exercise diabetic. Groups 2 and 3 received streptozotocin (37mg/kg) by intraperitoneal injection two weeks after the high-fat diet Diabetic training 5 times a week for 8 weeks run on a treadmill with duration and intensity that in the final weeks were 55 min / d and 26 m / min , respectively. 24 hours after the last exercise the prefrontal cortex of mice tissue samples of all groups were extracted and 5-HT (μg/g) and TPHconcentration was measured respectively by Elisa and Western Blotting from prefrontal cortex tissue samples. To evaluate the differences between the group of design, analysis of variance (ANOVA) and Tukey post hoc test at the significance level was less than 0.05 were used. Results: Statistical analysis showed that 5-HT levels in the diabetic group were significantly lower than the healthy control group (P=0.001) and exercise diabetic (P=0.009) and average 5-HT between control group and exercise diabetic has no significant difference. TPH results show that the average diabetic groups were significantly lower than the healthy control group (P=0.000). The results showed that the amount of TPH in the exercise diabetic group was significantly higher than the diabetic control group (P=0.000). Conclusion: In this study, diabetes reduces 5-HT in the prefrontal cortex. Some studies have shown that inflammation in type 2 increases the cytokines IL-6 and TNF-α, and these cytokines by increasing the activity of indolamine 2, 3 dioxygenase in the brain alters the metabolism of tryptophan and reduces the production of 5-HT. Chronic activity reduces systemic and tissue inflammation, thus increasing 5-HT in the brain. The reduction of TPH due to diabetes can also be the factors that affect in the decrease of prefrontal

The effect of Aerobic Training on Serotonin and Tryptophan Hydroxylase of Prefrontal Cortex in type 2 Diabetic Rats