Corydalis And Its Active Ingredient Dopamine System Against Morphine Addiction Action Mechanism And The Effect Is

Objective: To investigate the effects of corydalis yanhusuo and L-tetrahydropalma-tine(l-THP) on the levels of dopamine neurotransmitter(DA), dopamine transporter (DAT) andthe second dopamine receptor (D2R) in learning and memory-related brain areas,hippocampus and striatum, the DA, DAT and D2R were detected in conditioned placepreference (CPP) rats suffered from morphine. And comparation the degree of similarityand consistency of the pharmacological effects was also studied.Methods: The180rats were randomly devided into nine experimental groups: NScontrol group, model group, NS treatment group, three dosages of Corydalis yanhusuo andl-THP, with20rats for each group. The rats were trained in black compartments and whiteones (drug-paired compartment) with the increasing doses of morphine for10days(hypodermically injected from10mg·kg-1to100mg·kg-1). Models of CPP were validatedin those psychological dependence rats after48h training. The dopamine contents weredetected as soon as the materials of hippocampus and striatum are harvested from rats ofNS control group and model group. The DAT and D2R levels are measured by western blot.The high, medium and low dose group of corydalis yanhusuo are given yanhusuo2g·kg-1,1g·kg-1and0.5g·kg-1water extraction liquid respectively （which containsl-THP were0.274mg,0.137mg and0.137mg respectively），and the high, mediumand low dose group of l-THP were given l-THP3.76mg·kg-1,1.88mg·kg-1and0.94mg·kg-1lavage treatment respectively, NS treatment group were lavaged normalsaline for6days and they were killed after test of CPP, again tested DA levels andexpression of DAT and D2R Similar to the front of materials.Results:(1) Compared with NS control group, the prolonged detention time in modelgroup was observed. The reduction effects of CPP were observed in the groups of both Corydalis yanhusuo (2g·kg-1and1g·kg-1) and l-THP (3.76mg·kg-1and1.88mg·kg-1)subjected to medicine for6days (P <0.01).（2）Compared with the NS control group,higher values were detected of hippocampus and striatum in model group, higher contentof neurotransmitter dopamine was observed in the morphine dependent rats (P <0.01).Compared with the NS treatment group and the model group, the higher values includingin the contents of neurotransmitter dopamine were detected of hippocampus and striatum(P <0.01, P <0.05).（3）DAT: Compared with the NS control group, the differentialexpression levels of DAT reduced in hippocampus and striatum in model group. Comparedwith the NS treatment group and the model group, the DAT of Corydalis yanhusuo (2g·kg-1and1g·kg-1) and l-THP (3.76mg·kg-1and1.88mg·kg-1) increased in hippocampusand striatum (P <0.01).（4）D2R: Compared with the NS control group, the differentialexpression levels of D2R reduced in hippocampus striatum in model group. Comparedwith the NS treatment group and the model group, the of D2R of Corydalis yanhusuo (2g·kg-1and1g·kg-1) and l-THP (3.76mg·kg-1and1.88mg·kg-1) increased in hippocampusand striatum (P <0.01).Conclusion:(1) Learning and memory-related brain regions hippocampus and striatumwas another neuroanatomical sites of action in the treatment of mental dependence offumarate and l-THP, its mechanism was related to lowering its elevated DAneurotransmitter levels, and increasing the expression of DAT and D2R.（2）Corydalisyanhusuo could be play14-times roles in effect of l-THP. The similar effects wereobserved on the neurotransmitter dopamine, DAT and D2R in learning andmemory-related brain areas, hippocampus and striatum of the morphine-dependent rats. Objective: To study1-2components within Corydalis yanhusuo synergy with l-THP inthe Treatment of anti-morphine Addiction. It provide Multi-component Chinese Medicineexperimental basis, which can developed from single and compound given priority to withyanhusuo drug detoxification to develop the treatment effects of opioid addictioncomponent.Methods: The Naloxone-induced withdrawal jumps in the morphine-dependentexperimental mice model was established by injecting morphine in mice with the dose of50mg·kg-1and naloxone after3h. The l-THP, dehydrocorydaline and palmatine weremixed in an appropriate ratio based on the natural part of each component in Corydalisyanhusuo(l-THP:dehydrocorydaline:palmatine=1:2.31:0.46) to compare the effect of themixed-drug with that of l-THP(3mg·kg-1) on withdrawal symptoms and weightloss in themodel mice.Results:Compared with the physiological saline treatment group, morphine depen-dent experimental mice group showed a remarkably increase in jumping times andjumping rate and weightloss (P<0.01，P<0.05). l-THP treatment group showed the sameoutcomes as morphine-dependent experimental mice group. Compared with themorphine-dependent experimental mice group, mixed-drug treatment group showed aremarkably decrease in jumping times and jumping rate and weightloss (P<0.01，P<0.05).Conclusion: These results showed that there was synergistic efficacy ofdehydrocorydaline and palmatine with l-THP in the Treatment of anti-morphineAddiction.