| Objective To establish the rats model of different susceptibility of morphine-induced conditioned place preference(CPP) and investigate the time-point expression of dopamine D2 receptor(D2R) and dopamine transptor(DAT) located in the medial prefrontal contex(mPFC),nucleur accumben(NAc) and ventral tegmental area(VTA) in high and low CPP rats, thus to unveil the possible mechanism lead to the different CPP susceptibility.Methods 160 male Sprague-Dawley rats were randomly assigned into experiment group (n=130) and control group (n=30). Rats in experiment group were intraperitoneally administrated with morphine, twice a day for ten days, in an ascending dosage schedule, from 5 mg/kg per dose at the first day, to the 50 mg/kg per dose at the tenth day increasing 5 mg/kg per dose per day. Rats in control groups were correspondingly injected with same volume saline.CPP training was conducted with biased procedure, The experiment group were re-classified into two groups according to the numerical value of the CPP(the testing score minus that of the pretest):high preference group(HP group) and low preference group(LP group),each group account for 20% of the total rats.Further, according to the executed time-points after the last administration, each the HP and LP group was classified into 3-hour group (3H),72-hour group(JD3) and 14-day group(JD14) respectively. Withdraw signs of two groups were assessed at the 3-day withdrawal. At the time of 3 hours, 72 hours and 14 days after the final injection, rats were scarified and cardio-perfused, and the brains were removed and sliced up coronarily. The sections including VTA, NAc and mPFC were selected. The mRNA levels of D2R and DAT in the regions were estimated with in situ hybridization.Results 1.No significant difference of pretest scores staying at the non-preference chamber exist among the three groups(P>0.05),however, the test scores of the CPP minus the time stayed at pretest natural preference in the HP group was significantly higher than the LP group(P﹤0.05).2. The scores of total withdraw signs was significantly higher in 3-day withdrawal group of HP group than that of LP group(P﹤0.05). 3. The expression of D2R mRNA in HP group which 3 hours after the last injection were significantly lower that of in the control and LP group in all regions(F=158.80～247.30,P=0.000),and the difference between the HP and LP group was significant;In J3D group,the expression of D2R mRNA in the HP group were remarkly lower than the control and LP groups(F=27.03～155.52,P=0.000), difference between the HP and LP group was significant(P ﹤0.05).4. DAT mRNA:The expression of DAT mRNA in HP group which 3 hours after the last injection were significantly lower than that of in the control and LP group in all regions(P﹤0.05),and the difference between the HP and LP group was significant except in NAc;In J3D, the expression in the HP group were remarkly lower than the control and LP groups, difference between the HP and LP group was significan(tP﹤0.05)in mPFC and NAc;In J14D,there were no difference between 3 groups in mPFC;The expression of DAT mPFC in HP group were lower than the LP group(P﹤0.05),however there were no difference between LP and control group in NAC;There were no difference between HP and LP group in VTA .Conclusions 1.The chronic morphine treatment develop high conditioned place preference and low conditioned place preference in part rats,it suggests that the modeling of different susceptibility to morphine-induced CPP can be successfully established by this way. 2.The expression of D2R mRNA in HP group were lower than that in LP group in mPFC,NAc and VTA,it showed that lower expression of D2R mRNA related to the high susceptibility to morphine. 3.The expression of DAT mRNA in HP group were lower than that in LP group in mPFC,NAc and VTA,it showed that there were correlation between lower expression of DAT mRNA related to the high susceptibility to morphine. 4.It can be inferred that D2R and DAT maybe correlated closely and underlie the different susceptibility to morphine induced CPP. |
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