The effects of penehyclidine hydrochloride on the withdrawal syndrome and conditioned place preference of morphine dependent rats / 中华行为医学与脑科学杂志

ABSTRACT

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 ratsmorphine 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,800 AM) and saline( 1600 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.