Studies On Dependance Of Valeriana Jatamansi Jones By Toxicogenomics

Objective:To evaluate the drug physical dependence of the ethanol extract of Valeriana jatamansi Jones,which is anti-anxiety medicine.Method:We established physical dependence mice model through the way of long term usage of Diazepam,and comparised with the withdrawal symptoms,tailing rate and body weight change, the ethanol extract of Valeriana jatamansi Jones can be judged whether it will induce drug physical dependence.Moreover,we explored the mechanism of drug physical dependence through gene expression profiling.Results:Animal experiments result showed that mice with the administration of Diazepam appear obvious withdrawal symptoms,and it was more serious with time.The mice with the administration of Valeriana jatamansi Jones didn't show withdrawal symptoms obviously.The tailing rate of Diazepam goup increased with administration time,and compared with normal mice,their body weight were down significantly after withdrawl drug(P<0.01).The tailing rate of Valeriana jatamansi Jones groups were always low,and its body weight were change lightly.which were no significant difference compared with normal mice(P>0.05).Microarray results showed that long-term oral administration of diazepam, Valeriana jatamansi Jones high dose and low dose drugs had influence on the genes expression of mouse brain tissue, and these differentially expressed genes were involved in several GO functional classification and signaling pathway. Neuroactive ligand-receptor interaction signaling pathway is the most different pathway between each drug group.The closely related to drug-dependent genes-CHRM1,CHRM3,HTR1A,HTR2C,GABRA3 and GABRG6 were changed significantly, which were belong to neuroactive ligand-receptor interaction signaling pathway of Diazepam group. And Valeriana jatamansi Jones has lightly effect on these genes.Conclusions:The drug physical dependence mice model was successfully established by long term usage of Diazepam.The mice of high doses and low doses of Valeriana jatamansi Jones group didn't appeared significant drug physical dependence symptoms.Chronic administration of diazepam, high-dose and low dose of Valeriana jatamansi Jones have significant impact on the genes expression of mouse brain tissue,and on the neuroactive ligand-receptor interaction signaling pathway.The drug physical dependence induced by Diazepam was closely correlated with CHRM1, CHRM3, HTR1A, HTR2C, GABRA3 and GABRG6. And Valeriana jatamansi Jones has lightly effect on these genes, which suggests that Valeriana jatamansi Jones has low potentiality on drug physical dependence.