These dopaminergic changes are closely related to EW-induced anxiety and ethanol intake. The pharmacological reversal of reduced DA levels in the CeA ameliorates EW-induced anxiety in rats [6] and [7], DA D2 receptors (D2R) exhibit low sensitivity in the CeA of type 1 alcoholics [8], and chronic mild stress increases ethanol intake in genetically modified low D2R mice [9]. Based on such evidence, the rectification of dysregulation in the mesoamygdaloid DA system during EW appears to be a promising target for the treatment of EW-induced anxiety and alcoholism.

Korean Red Ginseng (KRG) is a steamed form of Panax ginseng Meyer with enhanced pharmacological activities that have beneficial effects for those with physical and mental exhaustion, including fatigue and anxiety [10] and [11]. KRG is also frequently prescribed to treat alcoholism, but the underlying pharmacological mechanisms have yet to be fully elucidated Selleck Metformin [12]. Experimental evidence suggests that improved neurotransmission in the brain is an important neuropharmacological mechanism supporting the effects of KRG. For example, Panax ginseng attenuates repeated cocaine-induced behavioral sensitization via the inhibition MEK inhibitor of elevated DA release in the nucleus accumbens [13] and ameliorates morphine withdrawal-induced anxiety and depression through the restoration of the balance

between corticotrophin releasing factor and neuropeptide Y in the brain [14]. Considering the critical role that mesolimbic DA plays in ethanol dependence and the similarities between ethanol and opiate addictions, the present study evaluated the possible anxiolytic effects of KRG during EW and the involvement

of the mesoamygdaloid DA system in this process. Adult male Sprague-Dawley rats (250–270 g) were obtained from Hyochang Science (Daegu, Korea) and acclimatized for 1 wk prior to the experimental manipulations. All rats were provided with ad libitum access to food and water and maintained at a temperature of 21–23°C, a relative humidity of 50%, and with a 12 h light/dark cycle CHIR 99021 throughout the course of the study. All procedures were conducted in accordance with the National Institutes of Health guidelines concerning the care and use of laboratory animals and were approved by the Animal Care and Use Committee of Daegu Haany University, Daegu, South Korea. This study used standardized KRG extract (KRGE) that was manufactured from the roots of 6-yr-old fresh ginseng (P. ginseng Meyer) provided by the Central Research Institute, Korea Ginseng Corporation (Daejeon, Korea). A high performance liquid chromatography (HPLC) fingerprint of the KRGE was developed ( Fig. 1A), and the KRGE contains 2.9 mg/g Rb1, 1.3 mg/g Rg1, 1.1 mg/g Rg3, and other ginsenosides. EW was induced in the experimental group via intraperitoneal (i.p.