多巴胺D2受体介导的神经通路对大鼠体内氯胺酮代谢动力学影响的研究

Objective to explore the effect of dopamine D2 receptor mediated neural pathway on the behaviours and pharmacokinetics of ketamine in rats. Method Male SD rats were divided randomly into ketamine addiction group,antagonistic group and control group.And conditions place preference (CPP) experiment were used to establish the ketamine addiction and antagonistic model.Meanwhile,the behaviors and the pharmacokinetics of ketamine in each groups of rats were investigated.After these models were established,the rats of three groups were all administered with Ketamine(10mg/kg).Then pharmacokinetic parameters were calculated.Result During the administration,ketamine addiction rats showed behavioral symptoms of excitement, fighting, genital congestion and so on.Contrarily antagonisitic rats didn't show the same condition,but gradually emergence the state of lethargy. Ketamine pharmacokinetics of the three groups are in line with the two-compartment model.Compared with the rats of control group, the t1/2α、t1/2Ka 、V1/F and Tmax of ketamine addiction rats were significantly higher. while Cmax and AUC(0-∞) were significantly lower (p＜0.05).Howere there were no significant differences in parameters between antagonistic group and control group except the t1/2βwas lower.Conclusion Compared with control group, ketamine addiction rats show that absorption and distribution of ketamine slow down,metabolic rate is faster,peak time prolongs and peak concentration decreased.And except for the slower metabolism, there were no significant differences between antagonistic group and control group. The result can provide theoretical and experimental support for further elucidating of ketamine addiction mechanism.