The Effect Of Corydaline And L-tetrahydropalmatine Against Morphine Dependence In Rats

OBJECTIVE To observe and compare the effect of corydaline and l-THP on the morphine-physical dependence and psychic dependence animal model and its possible mechanism.METHODS Nine days after the administration of morphine by dose escalation, different drug treatment were given 30 min before intraperitoneal administration of naloxone to observe the effect of monomer to withdrawal symptoms and weight; using locomotion test, the effect of drugs pretreatment on spontaneous activities induced by acute morphine and behavioral sensitization induced by increasing dosages of morphine were observed; using CPP test, the effect of drugs were observed by the CPP formation, expression, regression model which were induced by morphine. Animal model of precipitated withdrawal was represented by withdrawal sign score; locomotion test and behavioral sensitization were represented by distance of spontaneous activity; CPP tests were represented by CPP scores. After the test of CPP formation, all rats were decapitated, the materials of Hip, Str, PFC were harvested from rats’ brain, and the levels of Glu R1, Glu R2 and DRD2 were measured by western blotting.RESULT(1) 80mg/kg corydaline had no significant decrease on symptoms of precipitated morphine withdrawal, but 10mg/kg l-THP could significantly decrease withdrawal symptoms in rats.(2) 40, 80mg/kg corydaline and 5, 10mg/kg l-THP could reversed the trend of the weight loss induced by naloxone-precipitated morphine withdrawal in rats, but there was no significant difference.(3) Corydaline doses less than 20mg/kg and l-THP doses lower than 5mg/kg could have no effect on locomotion activity in rats within 60 min.(4) 5mg/kg corydaline and 2.5mg/kg l-THP significantly reduced morphine-induced high activity in rats.(5) On the animal model of the fomation of behavioral sensitization, 5mg/kg corydaline and 2.5mg/kg l-THP could markedly decrease high locomotion activity induced by morphine in rats.(6) 5mg/kg corydaline and l-THP doses lower than 1.25mg/kg showed a significantly decrease in the formation of morphine induced CPP scores in rats.(7) 5mg/kg corydaline and 2.5mg/kg l-THP could effectively reduce the expression of morphine-induced CPP scores.(8) Corydaline and l-THP could decrease the regression of morphine-induced CPP scores according to the dose compared to morphine group, but had no significant difference.(9) 5mg/kg corydaline and l-THP couldn’t cause CPP effects.(10) In the animal model of CPP formation, compared to the control group, the expression of Glu R1, Glu R2 in the Hip, Str, PFC brain regions had an upward trend in the morphine group, corydaline and l-THP had varying degrees to down-regulated their expression.(11) In the animal model of CPP formation, corydaline and l-THP could reverse the down-regulated expression of DRD2 in Str brain region which induced by morphine, and l-THP could also up-regulate the expression of DRD2 in PFC brain region in a dose-dependent manner.CONCLUSION Corydaline and l-THP had varying degrees of therapeutic effects on morphine physical dependence and psychic dependence; both of them couldn’t cause psychic dependence under experimental doses; they might up-regulate the expression of DRD2 in Str, PFC brain regions to play a role in anti-morphine CPP formation. L-THP had more prospects by the lower onset dose than corydaline.