Effect of Ginseng Saponins on Enhanced Dopaminergic Transmission and Locomotor Hyperactivity Induced by Nicotine

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 [ 3 H]raclopride to DA D 2 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 [ 3 H]raclopride to rat striatal membranes with an IC 50 of 5.1471.09 mM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [ 3 H]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 D 2 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.

Inhibitory Effects of Ginseng Total Saponins on Behavioral Sensitization and Dopamine Release Induced by Cocaine

“…16,21) The current results demonstrated that pretreatment with GTS had a strong inhibitory effect on cocaine-induced neurochemical and behavioral sensitization, which is consistent with previous studies showing that GTS suppressed the cocaine-induced conditioned place preference in mice and reduced behavioral activation induced not only by cocaine but also by other psychostimulants, such as methamphetamine, 36) morphine, 18) and nicotine. 21) Many studies have shown that pretreatment with GTS inhibited cocaine-induced hyperactivity as well as conditioned place preference in mice and the development of postsynaptic dopamine receptor supersensitivity. 16,37,38) Ginseng extract also inhibited the development of the reverse tolerance to the locomotor-acceleration effect of morphine, and the development of morphine-induced dopamine receptor supersensitivity and physical dependence.…”

“…Furthermore, they have shown that GTS inhibited the development of the postsynaptic dopamine receptor supersensitivity, 16,18,19) and blocked nicotine-induced behavioral activity. 20,21) However, the effects of GTS on cocaine-induced behavioral and neurochemical alterations have not been investigated. Therefore, in the present study, we examined whether GTS could affect repeated cocaine-induced behavioral sensitization and accumbal Fos-like immunoreactivity using immunohistochemical methods.…”

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

“…When the effects of total ginseng saponins were examined on presynaptic nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and on the in vitro and in vivo binding of [ 3 H]raclopride to DA D 2 receptors, inhibition of nicotine-induced DA release and D 2 receptor binding was observed along with behavioral inhibition of nicotine-induced sensitization [149]. Similar results were observed with repeated cocaine administration.…”

Wild Ginseng Attenuates Repeated Morphine-Induced Behavioral Sensitization in Rats

“…Their chemical and pharmacological properties have been reported by investigators in many countries. Recently, several studies suggest that Panax ginseng (PG) and its ginsenosides can act on the central dopaminergic system [7,13]. Many studies have also reported that Panax ginseng inhibited the hyperactivity and the conditioned place preference of morphine, cocaine, and methamphetamine [9][10][11].…”