Effects Of Small Complex Prescription Of Salvia Miltiorrhiza And Radix Astragali On Morphine Induced Conditioned Place Preference In Mice And Its Possible Mechanism

Objective: To extract and separate the effective fraction of Salvia Miltiorrhiza and Radix Astragali,then to determinate the content to control the quality of Salvia Miltiorrhiza and Radix Astragali;To optimize the best proportion of Salvia Miltiorrhiza and Radix Astragali by uniform-designed method in pharmacodynamics(conditioned place preference model was used in the study) and defined the best proportion by mathematic statistics. It has provided basis for their proportional use; To investigate the effect of small complex prescription of Salvia Miltiorrhiza and Radix Astragali on relapse behavior in morphine-dependent mice;To study the possible mechanism of the small complex prescriptionMethods:(1)The effective fraction of Salvia Miltiorrhiza and Radix Astragali was extracted and seperated.The content of cryptotanshinone in effective fraction of Salvia Miltiorrhiza was determinated by HPLC method,astragalosides in effective fraction of Radix Astragali was determinated by ultraviolet spectrophotometry.(2) Established a CPP model induced by morphine in mice,then selected the proportion of Salvia Mltiorrhiza and Radix Astragali by uniform-designed method and defined the best proportion by mathematic statistics on this CPP model.(3) Established a relapse model induced by morphine in mice,treated by administering (ip) small complex prescription of Salvia Miltiorrhiza and Radix Astragali to study the therapeutic action.(4) Dopamine content in the brain of mice was measured by RP-HPLC-Method with fluorescence detector.Results: (1) The cryptotanshinone content in effective fraction of Salvia Miltiorrhiza was 36.25 %, astragalosides content in effective fraction of Radix Astragali was 84.5 %.(2) The time of staying in morphine-paired white compartment was significantly increased,the strong place preference was observed in mice.It showed that the CPP model was reliable and stable.(3) The optimized dosage of Salvia Miltiorrhiza was 80 mg/kg and Radix Astragali was 41 mg/kg,they could notably depress CPP scores points in mice.The best proportion of Salvia Miltiorrhiza and Radix Astragali was 2:1.(4) Compared with morphine group,the time the mice treated with 60 , 120 mg/kg small complex prescription of Salvia Miltiorrhiza and Radix Astragali spent on the drug-paired side was significantly reduced(P <0.05)after priming injection of morphine (3 mg/kg).(5) The small complex prescription of Salvia Miltiorrhiza and Radix Astragali(60,120 mg/kg) could significantly inhibit DA output in the brain of morphine-dependent miceConclusion:(1) It would be possible to use uniform-design combined with pharmacyodynamics method in defining the optimal dosage of ingredients in complex prescription.(2) The best proportion of SmEf and RaEf was 2:1.The depress effect on the acquisition of morphine induced CPP in mice of SmEf and RaEf together used(120 mg/kg) was more notable than SmEf(80 mg/kg) or RaEf(240 mg/kg) single administration.Salvia Miltiorrhiza was the dominating drug and Radix Astragali played the synergy of promoting role in the complex prescription.(3) Small complex prescription of Salvia Miltiorrhiza and Radix Astragali has some effects on the inhibitory of relapse behavior by priming injection of morphine in morphine-dependent mice.(4) The mechanism of antagonism of small complex prescription of Salvia Miltiorrhiza and Radix Astragali on morphine psychic dependence may be related to the decrease of DA level in the brain of morphine-dependent mice.(5) Small complex prescription of Salvia Miltiorrhiza and Radix Astragali may be potentially useful in the treatment of opiate dependence.