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

Abstract

Cocaine is a potent and widely abused psychostimulant that exerts behavioral and neuropharmacological effects. Repeated exposure to psychostimulants, including cocaine, can produce behavioral sensitization, as evidenced by an enhanced locomotor response to a subsequent injection of the drug.1) Behavioral sensitization has been implicated in the development of drug addiction and in drug-induced psychosis.2)The mesolimbic dopamine (DA) system from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), one of the main central dopaminergic systems, has been implicated in the processes of drug addiction, including behavioral sensitization. 3,4) It has been demonstrated that the development of psychostimulant-induced behavioral sensitization is associated with alterations of neurotransmission in the mesolimbic dopamine pathway.5) For example, many studies have demonstrated that the reinforcing effects of cocaine are related to the blockade of the dopamine reuptake systems, 6) and the consequent increases in the binding of dopamine to its postsynaptic receptors.7) The inhibition of dopamine reuptake has been demonstrated in several brain nuclei, such as the NAc, the striatum, the VTA, and the medial prefrontal cortex.3,8-10) Dopamine receptor antagonists also block the cocaine-induced increases in locomotor activity and stereotypy, the decrease of food intake, 11) and they block the cocaine-induced reinstatement of drug seeking behavior. 12)Several studies have shown that repeated exposure to cocaine produced the expression of c-fos as a neuronal marker for postsynaptic activation and stimulates dopamine release in the NAc. 13,14) The root of Panax ginseng C. A. MAYER, ginseng, has been widely used as an herbal medicine around the world. The major components of ginseng are the ginsenosides (ginseng total saponins: GTS), which have a four-ring, steroid-like structure with sugar moieties.15) Their chemical and pharmacological properties have been reported by investigators in many countries. Moreover, GTS appears to be responsible for most of the pharmacological effects of ginseng. Recently, several studies have suggested that GTS and ginsenosides may act on the central dopaminergic system. 16,17) Many studies have also reported that GTS inhibited the hyperactivity and conditioned place preference of morphine, cocaine, and methamphetamine. 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. Also, we examined whether Korea; 505 Banpo-Dong, Seocho-ku, Seoul 137-701, South Korea. Received June 20, 2007; accepted November 2, 2007; published online December 20, 2007 Many stu...

Effects of ginseng saponin on acute cocaine-induced alterations in evoked dopamine release and uptake in rat brain nucleus accumbens

“…In contrast, the baseline DA release and cocaine-induced uptake inhibition are minimally affected by GTS. Overall, these results are consistent with previous microdialysis finding that GTS reduces cocaine-stimulated DA efflux in the rat nucleus accumbens (Lee et al, 2008). Importantly, the present study extends the microdialysis results by demonstrating that GTS inhibits cocaine-induced facilitation of the central DA neurotransmission by selectively attenuating the effects of cocaine on evoked (action potential-dependent) DA release but not on the uptake.…”

“…Finally, we have demonstrated a rebound release enhancement during acute withdrawal. Thus, multiple mechanisms might underlie cocaine-mediated potentiation of DA neurotransmission and behaviors as well as the “therapeutic” efficacy of ginseng against cocaine abuse (Volkow et al, 1997; Kiyatkin et al, 2000; Kim et al, 1995; Tokuyama et al, 1996; Lee et al, 2008). …”

“…In addition to interactions with the opioid systems, recent reports have demonstrated that GTS also attenuates cocaine- or amphetamine-induced behavioral activity such as hyperactivity and conditioned place preference (Kim et al, 1995; Tokuyama et al, 1996; Halladay, et al, 1999; Lee et al, 2008). Enhancement of the central dopamine (DA) neurotransmission may play an important role in mediating behavioral effects of psychostimulants (Lee et al, 2001).…”

Longitudinal changes of dopamine transporters in heroin users during abstinence

“…The underlying mechanism of L-THP may involve increases in the synthesis and release of endogenous opioid peptides (Chu et al 2008). Ginseng was previously reported to be effective at inhibiting the behavioral effects of drugs by possibly modulating the central dopaminergic system (Lee et al 2008(Lee et al , 2011. Clear mechanism(s) of action can hardly be attributed to a prescription constituted of a complex herbal mixture (with 15 different herbs and at least 101 compounds identified in a previous study) (Wang et al 2012).…”

Protective Effect of Korean Red Ginseng Extract on the Infections by H1N1 and H3N2 Influenza Viruses in Mice

“…3,4 Various beneficial pharmacological effects of ginseng or its components have been reported, including anticancer, anti-allergy, antiinflammatory, antifatigue, antistress, and immunomodulatory activities. [5][6][7][8][9][10][11][12][13][14][15][16] In clinical studies, ginseng has been shown to have beneficial effects on improving the survival and the quality of life among breast cancer patients, 17 in a placebocontrolled pilot trial of cancer patients, 18 in patients infected with human immunodeficiency virus, 19,20 and on reducing the occurrence of gastric cancer. 21 Immunomodulatory effects are among the beneficial properties attributed to ginseng extract.…”