Objective: To investigate the activity change of six kinds of cytochrome P450 (CYP450) subunit in the acute depression model rats induced by reserpine based on cocktail probe substrates method

in order to explore the pathogenesis of the depression from interaction of drug metabolism. Method: Based on the literatures at home and abroad to establish the acute depression model induced by reserpine

rats were randomly divided into the blank group

the model group and the venlafaxine group.Theophylline

chlorzoxazone

tolbutamide

dextromethorphan

omeprazole and midazolam were selected as probe substrates of CYP1A2

CYP2C6

CYP2D1

CYP2D2

CYP2E1 and CYP3A2 in rats

LC-MS/MS was developed for determining concentrations and pharmacokinetic parameters of six kinds of mixed probe in rats. Result: The concentration of tolbutamide in the model group rats increased significantly with slow metabolism

the concentration of midazolam in rats decreased significantly and metabolism accelerated.After administration of venlafaxine

concentrations of theophylline

chlorzoxazone and midazolam in rats increased significantly with slow metabolism. Conclusion: Acute depression model state induced by reserpine has strong inhibition effect on CYP2D1 and CYP2D2 in rats

and has strong induction on CYP3A2.Venlafaxine has strong inhibition effect on CYP1A2

CYP2C6

CYP2E1 and CYP3A2 in the model rats.