Effect of agmatine co-administration with yohimbine on morphine-induced behavioral sensitization in mice / 国际药学研究杂志

ABSTRACT

Objective To investigate the effect of agmatine or agmatine combined with yohimbine on morphine-induced psychological dependence in mice. Methods 1. Testing the effect of agmatine or agmatin combined with yohimbine on basal locomotor activity in 60 minutes. C57BL/6J male mice were divided into four groupscontrol group, agmatine (1,10,20,40 and 80 mg/kg) groups, yohimbine(0.3,1,2 and 8 mg/kg) groups and yohimbine(2 mg/kg)+ agmatine(80 mg/kg) group. 2. Testing the effects of drug pretreatment on morphine-induced hyperlocomotion in 60 minutes. Mice were divided into five groups control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg)+ morphine(10 mg/kg) group,yohimbine(2 mg/kg)+ morphine(10 mg/kg) group and yohimbine(2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. 3. Observing the effects of agmatine or agmatine combined with yohimbine on morphine induced behavioral sensitization. The mice were administrated with morphine(10 mg/kg) on the 1st , 4th and 7th day and the locomotor activity of mice was recorded for 60 minutes. Mice were divided into four groups control group, morphine(10 mg/kg) group, agmatine(1,20 and 80 mg/kg) + morphine(10 mg/kg) groups and yohimbine (2 mg/kg)+ agmatine(80 mg/kg)+ morphine(10 mg/kg) group. Results Our present study showed that agmatine(1-80 mg/kg) or yohimbine (0.3-2 mg/kg), a selective antagonist of α2-adrenoceptor, had no significant effect on basal locomotor and acute morphine-induced hyperlocomotion compared with those of control group. However, the distance in the group of agmatine combined with yohimbine followed by morphine for 60 min was(22 581.6±11 694.0) cm,which was significantly lower than the acute morphine group(37 577.9±9 657.4)cm(P<0.05). In the mophine-induced behavioral sensitization model, agmatine(1,20 and 80 mg/kg) alone had no effect on morphine-induced development of behavioral sensitization in mice. But, the combination of the two drugs significantly attenuated morphine-induced behavioral sensitization. The locomotor activities in the combination treatment groups were (21 112.7±5 586.7)cm,(37 672.7±10 518.8)cm and(47 681.0±15 845.3)cm, which were lower than those of morphine group (31 156.4±8 010.5) cm(P<0.01),(51 724.9±11 364.51)cm(P<0.05) and(63 572.2±12 151.2) cm(P<0.05) on the 1st , 4th and 7th day of experiment, respectively. Conclusion Our current results demonstrated that agmatine combined with yohimbine could decrease morphine-induced psychological dependence in mice. It may provide a new strategy for psychological dependence of morphine.