Modulatory effect of ginseng total saponin on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the rat.

ABSTRACT

Several studies have demonstrated that behavioral activation induced by psychostimulants is prevented by ginseng total saponin (GTS), which has been known to act on the central dopaminergic system. In an attempt to investigate whether the effect of GTS is through its inhibitory action on the elevated dopaminergic transmission, we examined the effect of GTS on nicotine-induced dopamine (DA) release in the nucleus accumbens (NA) of freely moving rats using in vivo microdialysis. Systemic injection of nicotine (3 mg/kg; i.p.) produced a mild increase in extracellular DA of dialysates samples in the NA (132+/-13% over basal levels at the peak). GTS (100 mg/kg; i.p.) had no effect on resting levels of extracelluar DA. However, an increase in accumbens DA release produced by systemic nicotine was completely blocked by systemic pre-treatment with GTS (100 mg/kg; i.p.). In addition, the effect of GTS on nicotine-induced tyrosine hydroxylase (TH) and immediate early gene expression in ventral tegmental area (VTA) or NA regions was examined. A single injection of nicotine increased TH mRNA level at VTA region. GTS, which did not affect the basal TH mRNA expression, attenuated nicotine-induced TH mRNA expression. Nicotine slightly increased both c-fos and c-jun mRNA level and GTS, which did not affect the basal c-fos and c-jun mRNA expression, further enhanced nicotine-induced c-fos and c-jun mRNA level at both VTA and NA regions. Our results suggest that GTS may have an inhibitory action against nicotine-induced DA release in NA region and TH mRNA expression in VTA region. GTS may exert an potentiative effect on both c-fos and c-jun mRNA expression at NA region through inhibiting the release of DA in NA.