Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in rats – Accepted Manuscript

Abstract: Background: Korean Red Ginseng is known to have anti-anxiety properties. This study was conducted to investigate the anxiolytic effects of Korean Red Ginseng extract (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid dopamine (DA) system in it.Methods: Rats were treated with 3 g/kg/day of ethanol for 28 days, and subjected to three days of withdrawal. During EW, KRGE (20 mg/kg/day or 60 mg/kg/day, p.o.) was given to rats once a day for three days. Thirty minutes after the final dose of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA). In addition, concentrations of DA and 3, 4-dihydroxyphenylacetic acid (DOPAC) in the central nucleus of the amygdala (CeA) were also measured by high performance liquid chromatography (HPLC).Results: The EPM test and RIA revealed KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective dopamine D2 receptor antagonist (eticlopride) but not by a selective dopamine D1 receptor antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of DA and DOPAC in a dose-dependent way. Additionally, western blotting and real-time polymerase chain reaction assays showed KRGE prevented the EW-induced reductions in tyrosine hydroxylase protein expression in the CeA and tyrosine hydroxylase mRNA expression in the ventral tegmental area.Conclusions: These results suggest KRGE has anxiolytic effects during EW by improving the mesoamygdaloid DA system.