The Study Of Synapse Plasticity Changes In Hippocampus CA3 Area And The Effects Of Expression Of NR1,NR2A Subunit In Heroin Dependent Rats

Objective To observe the long-term potentiation changes in hippocampus CA3 area and the Effects of expression of NMDA receptor NR1,NR2A subunit in heroin dependent rats. Methods Forty SD rats were randomly assigned into four groups: heroin dependent group, heroin+MK-801 group, heroin abstinence group and control group, Heroin was injected subcutaneously twice a day according to the principle of daily increasing dose in SD rats. On the tenth day the withdrawal signs precipitated by intraperitoneal injection of naloxone were evaluated and the heroin dependent model was established .After the model was established, heroin was injected continuously according to the maintenance dose of the heroin dependent group: Heroin+MK-801 group at each time injects the heroin 30 minutes after injection MK-801; Normal saline was injected in rats of the control group as the same way. Four groups were respectively conducted in Morris water labyrinth test, which was used to dect the learning and memory of rats. Population spike in CA3 region was recorded in vivo following stimulation of lateral perforant path ,For the induction of LTP , 4 trains (50 shocks/ t rain , 500 Hz) high-frequency tetanic stimulations were applied to lateral perforant path. The expression of NMDA receptor NR1 subunit mRNA was semi-quantitatively determined by reverse transcription-polymerase chain reaction (RT2PCR). Results 1. The withdrawal signs were consistent with the scoring indicators of the established heroin-addict model of rats.2. The escape latency and the searching distance of heroin dependence rats were significantly longer than the rats of control,heroin+MK-801and abstained groups in place navigation test(P<0.01).The explore time and the distance of original platform area in proportion to the total distance of heroin dependence rats were less than the heroin abstained group(P<0.05),less than the control and heroin+MK-801 group(P<0.01)in spatial probe test.3. After tetanic stimulation, the change rates of population spike in heroin abstinence group were significantly lower than heroin+MK-801 group, heroin dependent group and control group at 10,20,30,40,50,60,70 and 80 minutes, no significant difference was found in the heroin dependent group,heroin+MK-801 group and control group.4. Compares with the normal control group, a significant difference was found among three groups' NR1.,and the expression ascension is most obvious in the heroin dependent group, contrast the heroin abstinence group and the heroin+MK-801 group had a statistics significance (P<0.05), NR1 abstention to break the group and NR1 the heroin MK-801 group compares the not obvious difference; the heroin MK-801 group's NR2A expression reduces, the heroin abstinence group's NR2A expression ascends, compared with the control group (P<0.05), no the significance between the heroin dependent groupand the control group(P>0.05). Conclusion: 1. The heroin dependent group caused the big mouse study memory to drop.2. The LTP effect in big mouse of the heroin abstention damaged, the heroin dependent group seahorse CA3 area synapse transmission had the compatible change.3. NR1 expression had obvious ascension which maybe the NMDA acceptor the excitability toxic effect.4. The CA3 area NR2A expression on the rats of withdrawaling heroin ascended but reduced in the heroin dependent group which were dealed with MK-801.