Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats
Aim:To investigate the pharmacokinetics and dopamine/acetylcholine-releasing effects of ginsenoside Re (Re) in brain regions related to learning and memory, and to clarify the neurochemical mechanisms underlying its anti-dementia activity.Methods:Microdialysis was conducted on awake, freely moving adult male SD rats with dialysis probes implanted into the hippocampus, medial prefrontal cortex (mPFC) or the third ventricle. The concentrations of Re, dopamine (DA) and acetylcholine (ACh) in dialysates were determined using LC-MS/MS.Results:Subcutaneous administration of a single dose of Re (12.5, 25 or 50 mg/kg) rapidly distributed to the cerebrospinal fluid and exhibited linear pharmacokinetics. The peak concentration (Cmax) occurred at 60 min for all doses. Re was not detectable after 240 min in the dialysates for the low dose of 12.5 mg/kg. At the same time, Re dose-dependently increased extracellular levels of DA and ACh in the hippocampus and mPFC, and more prominent effects were observed in the hippocampus.Conclusion:The combined study of the pharmacokinetics and pharmacodynamics of Re demonstrate that increase of extracellular levels of DA and ACh, particularly in the hippocampus, may contribute, at least in part, to the anti-dementia activity of Re.