吗啡依赖大鼠海马长时程增强改变及归元片的干预效应

目的:在体观察吗啡条件性位置偏爱(conditioned place preference,CPP)大鼠海马齿状回(dentate gyrus,DG)长时程增强(long-term potentiation,LTP)的变化,评价归元片自身有无依赖性以及对吗啡CPP和LTP的干预效应。方法:(1)连续给予吗啡(5mg·kg-1)7d,使大鼠产生明显的吗啡CPP,观察吗啡CPP的自然消退;(2)归元片(25mg·kg-1及50mg·kg-1)训练7d,d8测定大鼠对伴药箱的偏爱效应;(3)在归元片干预实验中,干预组在每次给予吗啡前15min分别给予不同剂量归元片(25、37.5mg·kg-1),观察归元片对吗啡CPP形成的影响。在以上模型的基础上,应用在体脑立体定位胞外记录技术测量海马齿状回LTP的变化。结果:(1)5mg·kg-1吗啡诱导大鼠对伴药侧产生显著性CPP;(2)归元片不能诱导大鼠形成CPP,同时也不影响DG-LTP;(3)吗啡CPP大鼠在高频刺激(high frequency stimulation,HFS)后,各时间点所记录的群体峰电位(population spikes,PS)相对幅值较对照组显著增高;(4)归元片25和37.5mg·kg-1均可拮抗吗啡CPP的获得,并能抑制吗啡对PS相对幅值的影响;(5)吗啡CPP在停用吗啡后12d消退,此时海马PS相对幅值与对照组比较无差异。结论:吗啡可诱导CPP,海马LTP在CPP形成时增强,在CPP消退后恢复正常,提示LTP参与药物成瘾过程。归元片自身不能诱导CPP,但可抑制吗啡CPP的获得与LTP的增强。

CHANGES IN AND EFFECTS OF GUIYUAN TABLETS ON LONG-TERM POTENTIATION OF MORPHINE DEPENDENT RATS

Objective:To investigate the changes in the long-term potentiation(LTP)at dentate gyrus(DG)granular cell synapses of chronic morphine treated rats in vivo. Guiyuan tablets were tested for psychological dependence producing potential and the effect on the conditioned place preference(CPP)induced by morphine and the LTP. Methods:(1)Rats were administered with morphine(5 mg·kg-1, once a day, sc) for 7 days to establish morphine CPP model, then the rats of CPP model were observed for the maintenance of CPP and the changes of DG-LTP at that time; (2) Tow groups of rats were trained separately with Guiyuan tablets(25 mg·kg-1 and 50 mg·kg-1, sc) for 7 days, and on d8, they were tested to see if the rats had Guiyuan tablets CPP and the changes in DG-LTP; (3) In another CPP model with Guiyuan tablets intervention, the intervenient groups of rats were pretreated with Guiyuan tablets (25 and 37.5 mg·kg-1, sc) 15 min before each injection of morphine during the 7 days training phase to observe the effect of Guiyuan tablets on acquisition of CPP and the changes of DG-LTP. Results:(1)5 mg·kg-1 morphine(sc) induced a significant CPP in rats;(2)Two different doses of Guiyuan tablets did not induce CPP and affect dentate gyrus(DG) -LTP of hippocampus in the rats;(3)The correspondence amplification of population spikes(PS) at each point of time and average PS amplitude post- high frequency stimulation (HFS)at DG of the rats in vivo from the morphine group was stronger;(4)Guiyuan tablets(25,37.5 mg·kg-1)blocked the development of morphine -induced CPP and inhibited the enhancement effect of morphine on PS amplitud;(5)The CPP of rats induced by morphine disappeared on day 12 after stopping administering morphine. When CPP disappeared,the phenomenon of the enhancement of PS was not discovered. Conclusion:Guiyuan tablets can antagonize the acquisition of morphine induced CPP without producing CPP themselves. The enhancement facilitation of LTP induced in morphine dependence rats can be inhibited by Guiyuan tablets,so hippocampal LTP is related with drug addiction to some degree.