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Effect of SCH23390 on Morphine withdrawal response and synaptophysin expression |
TANG Shan ZHOU Shengquan LIU Qiaofeng▲ |
Department of Pathology and Pathophysiology, Chengdu Medical College, Sichuan Province, Chengdu 710083, China |
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Abstract Objective To study the effect of dopamine D1 receptor antagonist SCH23390 on Morphine withdrawal response and synaptophysin (SYN) expression. Methods According to the random number table method, 40 rats were divided into control group, Morphine group, SCH23390 group and SKF38393 group, with 10 rats in each group. Rats in Morphine group, SCH23390 group and SKF38393 group were injected with Morphine in increasing doses for 5 days to establish Morphine-exposure animal models. Rats in SCH23390 group and SKF38393 group were injected with 0.5 μL 10 mmol/L SCH23390 or 0.5 μL 5 mmol/L SKF38393 into the midbrain periaqueductal gray 15 min before intraperitoneal Morphine injections on the mornings of days 1-4. On the 5th day, all rats were injected with Naloxone to observe withdrawal response, and SYN level was detected by immunohistochemistry and Western blotting. Results Withdrawal response total score and scores of tooth tremor, diarrhea, abnormal posture, squinting and wet dog shaking in Morphine group were higher than those in control group, and the differences were statistically significant (P < 0.05 or P < 0.01). Withdrawal response total scores and scores of tooth tremor and diarrhea in SCH23390 group were lower than those in Morphine group, and the differences were highly statistically significant (P < 0.01). There was no significant difference in withdrawal response total scores and scores of tooth tremor, diarrhea, squinting and wet dog shaking between SKF38393 group and Morphine group (P > 0.05); while score of abnormal posture of SKF38393 group was higher than that of Morphine group, and the difference was statistically significant (P < 0.05). The expression level of SYN protein in Morphine group was higher than that in control group, and the difference was highly statistically significant (P < 0.01). The expression level of SYN protein in SCH23390 group was lower than that in Morphine group, and the difference was statistically significant (P < 0.05). The expression level of SYN protein in SKF38393 group was higher than that in Morphine group, and the difference was statistically significant (P < 0.05). The number of SYN positive neurons in Morphine group was higher than that in control group, and the difference was highly statistically significant (P < 0.01). The number of SYN positive neurons in SCH23390 group was lower than that in Morphine group, and the difference was statistically significant (P < 0.05). The number of SYN positive neurons in SKF38393 group was higher than that in Morphine group, and the difference was statistically significant (P < 0.05). Conclusion SCH23390 reduces the Morphine withdrawal response, possibly by downregulating SYN.
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