Ginsenosides attenuate methamphetamine-induced behavioral side effects in mice via activation of adenosine A2A receptors: Possible involvements of the striatal reduction in AP-1 DNA binding activity and proenkephalin gene expression

Eun Joo Shin, Toshitaka Nabeshima, Hong Won Suh, Wang Kee Jhoo, Ki Wan Oh, Yong Kwang Lim, Dong Sup Kim, Ki Hwan Choi, Hyoung Chun Kim

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Current evidence suggests that ginsenosides inhibit methamphetamine (MA)-induced changes in behavior, but the precise mechanisms that underlie this effect are yet to be determined. We examined the role of adenosine receptors in the ginsenoside-induced changes in hyperlocomotion and conditioned place preference (CPP) in mice that occurred in response to administration of MA (2 mg/kg, i.p. × 1 or 2 mg/kg, i.p. × 6). Changes in circling behavior paralleled changes in CPP in the presence of MA. Pre-treatment with ginsenosides (50 or 150 mg/kg, i.p.) attenuated the MA-induced circling behavior and CPP. This attenuation was reversed by the adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chrostyryl)xanthine (CSC; 0.5 and 1.0 mg/kg) in a dose-dependent manner, but neither the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 0.5 and 1.0 mg/kg) nor the A2B receptor antagonist alloxazine (ALX; 1.5 and 3.0 mg/kg) had any such effect. MA-induced increases in activator protein (AP)-1 DNA binding activity, Fos-related antigen immunoreactivity (FRA-IR), proenkephalin mRNA expression, and proenkephalin-like immunoreactivity were reduced consistently in the striatum of animals that were pretreated with ginsenosides. These reductions were largely prevented by CSC, but not by CPT or ALX. Our results suggest that the stimulation of A2A receptors by ginsenosides attenuates the changes in behavior and the increases in AP-1 DNA binding activity, FRA-IR, and proenkephalin gene expression in mouse striatum that are induced by MA.

元の言語English
ページ(範囲)143-157
ページ数15
ジャーナルBehavioural Brain Research
158
発行部数1
DOI
出版物ステータスPublished - 07-03-2005
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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