Abstract
Several studies have shown that behavioral hyperactivity induced by psychomotor stimulants is prevented by ginseng saponins. In an attempt to investigate whether the effect of ginseng saponins is through their inhibitory action on the enhanced dopaminergic transmission by psychomotor stimulants, we examined the effects of ginseng total saponin (GTS) presynaptically on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and postsynaptically on the in vitro and in vivo binding of [3H]raclopride to DA D2 receptors. Also, we examined the effects of GTS on nicotine-induced locomotor hyperactivity and on nicotine-induced Fos protein expression in the nucleus accumbens and striatum. Systemic pretreatment with GTS (100 and 400 mg/kg, intraperitoneally (i.p.)) resulted in a dose-dependent inhibition of locomotor hyperactivity induced by nicotine. GTS decreased nicotine-induced DA release in the striatum in a dose-dependent manner. However, GTS had no effects on resting levels of locomotor activity and extracellular DA in the striatum. GTS inhibited the in vitro binding of [3H]raclopride to rat striatal membranes with an IC50 of 5.14±1.09 μM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [3H]raclopride in the striatum. GTS decreased nicotine-induced Fos protein expression in the nucleus accumbens and striatum, reflecting the inhibition by GTS of nicotine-induced enhancement of dopaminergic transmission. The results of the present study suggest that GTS acts not only on dopaminergic neurons directly or indirectly to prevent nicotine-induced DA release but also postsynaptically by binding to DA D2 receptors. This may explain the blocking effect of GTS on behavioral activation induced by nicotine and conceivably by other psychostimulants. Our data raise the possibility that GTS, by attenuating nicotine-induced enhancement of dopaminergic transmission, may prove to be a useful therapeutic agent for nicotine addiction and warrant further investigation on its effect on nicotine's rewarding property.
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Acknowledgements
This study was supported by grants from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea (M103KV010016-04K2201-01630) and the Biomedical Brain Research Center, Ministry of Health and Welfare, Republic of Korea (01-PJ8-PG6-01NE01-0003).
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Kim, S., Shim, I., Chung, JK. et al. Effect of Ginseng Saponins on Enhanced Dopaminergic Transmission and Locomotor Hyperactivity Induced by Nicotine. Neuropsychopharmacol 31, 1714–1721 (2006). https://doi.org/10.1038/sj.npp.1300945
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DOI: https://doi.org/10.1038/sj.npp.1300945
