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

Several studies have demonstrated that behavioral activation induced by psy chostimulants is prevented by ginseng total saponin (GTS), which has been k nown to act on the central dopaminergic system. In an attempt to investigat e whether the effect of GTS is through its inhibitory action on the elevate d dopaminergic transmission, we examined the effect of GTS on nicotine-indu ced dopamine (DA) release in the nucleus accumbens (NA) of freely moving ra ts using in vivo microdialysis. Systemic injection of nicotine (3 mg/kg; i. p.) produced a mild increase in extracellular DA of dialysates samples in t he NA (132 +/- 13% over basal levels at the peak). GTS (100 mg/kg; i.p.) ha d no effect on resting levels of extracelluar DA. However, an increase in a ccumbens 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 g ene 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-indu ced TH mRNA expression. Nicotine slightly increased both c-fos and c-jun mR NA level and GTS, which did not affect the basal c-fos and c-jun mRNA expre ssion. 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 ac tion against nicotine-induced DA release in NA region and TH mRNA expressio n in VTA region. GTS may exert an potentiative effect on both c-fos and c-j un mRNA expression at NA region through inhibiting the release of DA in NA. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.