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Objective: To observe the action of Salvia miltiorrhiza extracts (SmE2, liposoluble constituents) on the formation of physical dependence induced by morphine in mice and the effects of SmE2 on the production of cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) in brain of morphine-dependent mice. Methods: Morphine-dependent mice model was established by sc injection of morphine at a gradual increasing dosage. The effect of SmE2 on the withdrawal symptoms induced by Naloxone in morphine-dependent mice was observed. cAMP and NO content in brain were determined through radioimmunoassay and nitrate reductase, respectively. Results: SmE2 (80 mg/kg) could remarkably reduce the withdrawal symptoms in morphine-dependent mice. The cAMP concentration in brain showed no obvious change in morphine-dependent mice treated with SmE2, but NO content in brain could significantly be reduced. Conclusion: SmE2 has effect on relieving the withdrawal symptoms in morphine-dependent mice with down-regulation of NO content in brain as possible mechanism.
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Objective To explore the effects of penehyclidine hydrochloride (PHC) on the withdrawal syndrome and conditioned place preference(CPP) of morphine dependent rats. Methods ( 1 ) Forty-eight male SD rats were randomly assigned to 6 groups with one of 8 rats:morphine dependent group (MOR group) ,naloxone precipitated withdrawal group ( NAL group) ,PHC treatment groups ( PHC1,2,3 ) ,normal saline control group ( NS group). Subcutaneous injection of morphine in gradually increasing doses for 5 days (from 10 to 50 mg/kg ,two times daily) to establish the model of morphine physical dependent rats. The withdrawal syndrome was precipitated by naloxone (5 mg/kg,sc) and treated with PHC in various doses (0.5,1.0,1.5 mg/kg ,ip ) 30 min before haloxone-precipitated withdrawal. The body weight loss and withdrawal syndrome were observed respectively in 20 minutes. (2) 40 male SD rats were randomly assigned to 5 groups with one of 8 rats: morphine dependent group (MOR group) ,PHC treatment groups (PHC1 ,2,3 ) ,normal saline control group (NS group). The morphine conditioned place preference was induced by alternate subcutaneous injection of morphine for 7 days in rats ( 10mg/kg,once daily,8:00 AM) and saline( 16:00 PM). At d8,the rats were received the CPP test. The rats of PHC groups were treated with PHC (0.5,1.0,1.5 mg/kg , ip) prior to the CPP test, whereas the rats were treated with saline in MOR and NS group. Results (1) Theweight loss((8.53 ±l.20)g,(7.36±l.06)g,(5.40±1.79 ) g vs ( 12.63 ± 2.22 ) g, F = 83.16, P ＜ 0.01 ) and score precipitated withdrawal symptoms ( 25.36 ± 3.11,21.38±3.50,17.06±1.78 vs 31.69 ±2.76, F=256.56, P＜0.01)of morphine withdrawal rats was obviously alleviated by ip PHC in dose-related manner before naloxone-precipitated withdrawal. (2) There were significant differences in the times spent in the drug-paired side (gray area) between MOR and PHC groups( (529 ± 83 )s,(460 ± 107 ) s, (418 ± 97 ) s vs ( 643 ± 111 ) s, F = 13.22, P ＜ 0.01 ), and also in dose-related manner. Conclusion PHC could significantly inhibit the withdrawal syndrome and the expression of CPP on morphine dependent rats in a dose-dependent manner.
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Objective: To evaluate the effect of RBa-I, an extract of Rosa bracteata Wend1, against withdrawa1 syndrome in morphine-dependent rats and to explore its mechanism. Methods: The mode1 rats of morphine dependent were established. The scores of withdrawa1 syndrome,?-EP level in hypotha1amus and pituitary body were observed to evaluate the effect of RBa-I in rats. Results: RBa-I can antagonize the urging withdrawa1 syndrome in morphine-dependent rats (ora1ly, 5 mg?kg -1 ), and the effect was inferior to chlonidine (oral1y, 0.2 mg?kg -1 ). It can a1so antagonize the natural withdrawal syndrome, decrease the tota1 scores of withdrawa1 syndrome and inhibit the decreasing of body weight. After a seven-day treatment course, the tota1 scores of withdrawa1 syndrome were decreased remarkab1y. The content of ?-EP in hypotha1amus and pituitary body were increased. Conclusion: RBa-I can antagonize the withdrawa1 syndrome of morphine-dependent rats and this may be related to the increase of ?-EP level in hypothalamus and pituitary body in rats.
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Objective:To explore the possible role of ? endorp hi n in effect of melatonin on morphine withdrawal symptoms in rats.Method:Acute model of morphine dependent rat was estalished by gradually increasing the dose of morphine through subcutaneous injections.CSF(cerebrospinal fluid)w a s got by push-pull perfusion and intracerebroventricular injection(icv)in a fixe d tuber.Concentration of ? endorphin in CSF was determined by radioimmunoassa y (RIA).Results:(1)The symptoms of natural morphine withdrawal were r e lieved significantly by icv ? Endorphin with a dose dependent manner.(2)The s y mptoms of natural morphine withdrawal were also relieved by ip melatonin.(3)The CSF ? endorphin level was significantly lower in morphine dependent rats than normal control,but that was higher in natural morphine withdrawal rats.That was also much more increased by ip melatonin in the withdrawal rats than in morphine dependent rats or normal control.Conclusion:The withdrawal symptom s could be relieved by icv ? endorphin or by ip melatonin in morphine dependetn rats.The mechanism may be partly due to the elevation of endogenous ? endorp hin level in brain of rats in withdrawal