The Studies Of Active Ingredients From Radix Astragali On Conditioned Place Preference In Mice Induced By Morphine

Objective:To Screen for active ingredient against morphine-induced psychic dependence in Radix Astragali through activity-guided tracing methods.To set up preliminary identification of active ingredient and study the possible mechanism of the action.Methods:(1)Established a morphine-induced conditioned place preference(CPP) model in mice,then Screened for active ingredient against morphine-induced psychic dependence in Radix Astragali through this model.(2)Observed the effects of the active ingredient on the acquisition and expression of morphine-induced CPP in mice. The self-dependence effect of the active ingredient was also evaluated.(3)The active ingredient against morphine-induced psychic dependence of Radix Astragali was identified by TLC and HPLC.(4)Cyclic adenosine monophosphate(cAMP) content in the brain of mice was measured by radioimmunoassay.Nitric oxide(NO) output in the brain was assessed by nitrate reductase method.Results:(1) Morphine(6 mg/kg,sc)induced mice to obtain a significant CPP,and the CPP model was reliable and stable.(2)AST3,an active ingredient of Radix Astragali could attenuate the CPP effect. (3)By pretreating with AST3(30,60 mg/kg) before each injection of morphine during the training phase, the CPP induced by morphine were antagonized remarkably(P<0.05, P<0.01).When AST3(80 mg/kg) was administered only once 30 min before the testing,the expression of CPP was also inhibited(P<0.01).AST3(80 mg/kg)itself did not induce CPP in mice.(4)The major element of AST3 was Astragaloside IV identified by TLC and HPLC.(5)AST3(60 mg/kg)could lowered cAMP content in the brain of morphine-dependence mice to a certain extent(P<0.05), AST3(30,60 mg/kg)could also significantly inhibit NO output in the brain of morphine-dependence mice(P<0.01). Conclusion:(1)AST3 may be the active ingredient that can antagonize the CPP effect induced by morphine. (2)AST3 could restrain the acquisition and expression of morphine-induced CPP in mice to a certain extent,and has no potential of psychic dependence.(3)The major element of AST3 was Astragaloside IV.(4)The mechanism of antagonism of AST3 on morphine psychic dependence may be related to the decrease of cAMP and NO level in the brain of morphine-dependence mice.(5)AST3 may be potentially useful in the treatment of opiate dependence.