Blockade of nicotine sensitization by methanol extracts of Glycyrrhizae radix mediated via antagonism of accumbal oxidative stress.

BACKGROUND: We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. METHODS: Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing. During the 4-d withdrawal period, the rats were treated once a day with MEGR (60 or 180 mg/kg/d). Extracellular DA levels were measured by in vivo microdialysis, the malondialdehyde levels and the activities of superoxide dismutase and catalase in the Nacc were biochemically evaluated, and the expression of antioxidant proteins was confirmed by Western blot assays. All data were assessed with analysis of variance tests followed by post-hoc comparison tests and p values <0.05 were considered statistically significant. RESULTS: The expression of repeated nicotine-induced locomotor sensitization was dose-dependently attenuated by MEGR, and 180 mg/kg/d MEGR significantly inhibited augmented accumbal DA release induced by a direct local challenge of nicotine. Moreover, 180 mg/kg/d MEGR reversed increases in malondialdehyde production, decreases in superoxide dismutase and catalase activities, and the reduced expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1 in the nicotine-sensitized Nacc. CONCLUSIONS: These results suggest that MEGR inhibited nicotine-induced locomotion and dopaminergic sensitization via antioxidant action.

Glycyrrhizae radix methanol extract attenuates methamphetamine-induced locomotor sensitization and conditioned place preference.

Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced by acute psychostimulants in rodents via GABAb receptors. This study investigated the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated methamphetamine- (METH-) induced locomotor sensitization and conditioned place preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6 consecutive days, subjected to 6 days of withdrawal, and then challenged with the same dose of METH to induce locomotor sensitization; during the withdrawal period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort of rats was treated with either METH or saline every other day for 6 days in METH-paired or saline-paired chambers, respectively, to induce CPP. These rats were also administered MEGR (180 mg/kg) prior to every METH or CPP expression test. Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH-induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR significantly inhibited the development and expression of METH-induced CPP. Furthermore, administration of a selective GABAb receptor antagonist (SCH50911) prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae Radix blocked repeated METH-induced behavioral changes via GABAb receptors.