The aim of this study was to investigate the potential antidepressive-like effect of tetramethylpyrazine (TMP), one of available blood-activating and stasis-eliminating components from traditional Chinese medicines, in chronic mild stress (CMS)-induced rat model of depression. Male Sprague-Dawley (SD) strain rats were divided into six matched groups (n = 13 or 14 in each group) based on their sucrose consumption: control, CMS, CMS + fluoxetine (FLU), and CMS + TMP groups. The rats except control were housed separately in different rooms, and the rat model of depression was established by exposing to an unpredictable sequence of stressors for 28 days; the rats in CMS + FLU were exposed to CMS and received administration of FLU (2.0 mg/kg/d, ig) for 28 days; the rats in CMS + TMP groups were exposed to CMS and received administration of TMP (10, 20, 40 mg/kg/d, ig), respectively, for 28 days. The rats in control group were given ordinary daily care, and the rats in control and CMS groups received ig administration of normal saline instead of FLU or TMP. The body weight, food intake and fluid consumption were measured, and the behaviors were examined by open field test before and after CMS, and forced-swimming test was performed 1 day after last unpredictable stressor. Chronic administration of TMP partially reversed the effects of CMS on consumption of sucrose solution and locomotion and exploration behavior, and potently shortened the immobility time during forced-swimming test following CMS in rats. The results showed that long-term administration of TMP partially reversed the effects of CMS on the body weight gain, the consumption of sucrose solution, the squares crossin gand rearing in open field test, and the immobility time during forced-swimming test in rats. The present data provide evidences that TMP possesses obvious antidepressant-like activity in CMS-induced rat model of depression.
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