Abstract
BackgroundWe 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.MethodsMale 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.ResultsThe 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.ConclusionsThese results suggest that MEGR inhibited nicotine-induced locomotion and dopaminergic sensitization via antioxidant action.
Highlights
We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamineinduced locomotor sensitization and conditioned place preference in rats
The present study showed that there was an increase in MDA production, reduced superoxide dismutase (SOD) and CAT activities, and decreases in the expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the nicotine-sensitized Nacc shell (NaccSh); these changes were all ameliorated by 180 mg/ kg/d MEGR
These results indicate that repeated nicotine treatment (RNT) elicits dysregulation in the Nrf2–HO-1 pathway and that the disturbance in cellular antioxidant function underlies the enhancement of accumbal oxidative stress which, in turn, further mediates RNT-induced behavioral and neurochemical sensitization
Summary
We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamineinduced locomotor sensitization and conditioned place preference in rats. RNT leads to a sensitized dopaminergic state such that a challenge dose of nicotine in a subject pre-exposed to nicotine produces a significant augmentation in accumbal DA release compared with a subject naive to nicotine [6]. This process is thought to be the neurobiological underpinning of behavioral sensitization. It is possible that the increase in accumbal oxidative stress induced by repeated administration of drugs of abuse might be a promising target for the treatment of addiction
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