【Animal modeling】-Effect of ginseng polysaccharide on behavior and ERK/c-fos pathway in prefrontal cortex of ethanol-induced behavioral sensitization mice

  Objective: To study the effect and possible mechanism of ginseng polysaccharide on ethanol-induced behavioral sensitization.

  Methods: Eighty KM mice were randomly divided into five groups, blank group, model group, GSP low-dose group (100 mg/kg), GSP medium-dose group (200 mg/kg) and GSP high-dose group (400 mg/kg). Except for the blank group, the other groups could freely ingest water or ethanol, and the ethanol concentration gradually increased with time (3%-12%, increasing by 3% every 4 days). This establishes a behavioral sensitization model for active ethanol uptake. The ethanol consumption and autonomic activity of each group were measured every day during the experimental period; the opening experiment was performed during the transformation period; the expression of behavioral sensitization was measured during the expression period. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of MDA and the activities of SOD and CAT in the prefrontal cortex. The protein expressions of ERK, pERK and c-fos in the prefrontal cortex were detected by Western blot. The mRNA expressions of p-ERK and C-FOS in the prefrontal cortex were detected by real-time quantitative PCR (Real-timePCR).

  RESULTS: Three doses of GSP significantly reduced the increase in autonomic activity induced by 9% and 12% ethanol during the formative period, and significantly inhibited the increase in autonomic activity and ethanol intake induced by the initial dose of 3% alcohol challenge (day 25). The middle and high doses of GSP can significantly reduce the number of crawling and standing in the opening test. GSP significantly inhibited the alcohol-induced increase of MDA levels in the prefrontal cortex and increased the activities of SOD and CAT. The results of Westernblot and Real-time PCR experiments showed that GSP could down-regulate the overexpression of p-ERK and c-fos protein and mRNA in the prefrontal cortex.

  Conclusion: GSP has inhibitory effects on ethanol-induced behavioral sensitization and ethanol uptake in mice, which may be by interfering with the ERK/c-fos pathway.