| Objective:The present study was aimed to observe the effects of D-serine on the learning and memory functions of the MK-801-induced schizophrenia model rats,and the related electrophysiological mechanisms were also concerned.Methods:Sixty male adolescent SD rats were randomly assigned into 6 groups(n =10):normal group(C),saline group(NS),MK-801 group(MK),MK-801 and D-serine low dose group(MK+D1),MK-801 and D-serine high dose group(MK+D2),and MK-801 and risperidone group(MK+RIS).Rats in normal group received no treatment,and rats in saline group were exposed to saline(1ml/kg,ip,qd)for 14 days,while other rats were all exposed to MK-801(0.2mg/kg,ip,qd)for 14 days,and all the rats were tested by the open field test,forced swimming test,and Y-maze behavior test.Since then,rats in saline group and MK-801 group received normal saline(1ml/kg,ip,qd),but the rats in other 3 groups were treated with D-serine(400mg/kg,800mg/kg,ip,qd)and risperidone(1mg/kg,ig,qd)for 10 days.After that,the behavior tests were repeated,and the learning and memory functions were evaluated by Morris water maze.Finally,the isolated rat hippocampal slices were prepared from these rats,and the electrophysiological parameters,excitatory postsynaptic potential(EPSP)and its long-term potentiation(LTP)were recorded and analyzed by intracellular recording techniques from CA1 pyramidal neurons.Results:1.The comparisons of open-field test resultsThe open-field test of 6 groups before drug intervention showed that,outside distance,total distance and distance in period T1,T2,T3 in Group MK,Group MK+RIS,Group MK+D1,and Group MK+D2 were higher than Group C and Group NS(P<0.05 or P<0.01).After drug intervention,outside distance,total distance and distance in period T1,T2,T3 in Group MK was also higher than Group C,Group NS(P<0.05 or P<0.01),while Group MK+RIS,Group MK+D1,Group MK+D2 were lower than those before drug intervention(P<0.05 or P<0.01)and Group MK(P<0.05 or P<0.01).2.The comparisons of forced swimming test resultsThe forced swimming test of 6 groups before drug intervention showed that,immobility time in Group MK,Group MK+RIS,Group MK+D1,and Group MK+D2 were longer than Group C and Group NS(P<0.01).After drug intervention,immobility time in the forced swimming test in Group MK was also longer than Group C and Group NS(P<0.05),while Group MK+RIS,Group MK+D1,Group MK+D2 were shorter than those before drug intervention(P<0.01)and Group MK(P<0.05 or P<0.01).3.The comparisons of Y-maze test resultsThe Y-maze test of 6 groups before drug intervention showed that,spontaneous alternation in Group MK,Group MK+RIS,Group MK+D1,and Group MK+D2 were less than Group C(P<0.05).After drug intervention,spontaneous alternation in Y-maze test in Group MK was also less than Group C and Group NS(P<0.05),while Group MK+RIS,Group MK+D1,and Group MK+D2 were higher than those before drug intervention(P<0.01)and Group MK(P<0.01).4.The comparisons of Morris water maze test resultsThe escape latency of 6 groups in the place navigation test during 7 test days showed that,test days(P<0.01)and animal groups(P<0.05)were significantly different,and the comparisons of SNK-q presented a significant difference between Group MK+D2 and Group MK,Group MK+RIS,Group MK+D1,or Group C(P<0.05 or P<0.01).There were also significant differences among 6 groups in test day 3(P<0.05),and between Group MK+D2 and Group MK or Group C(P<0.01).The movement distance analysis showed significant differences among 6 groups in test day 3(P<0.05),and between Group MK+D2 and Group MK or Group C(P<0.01)either.And the ratio of strategic analysis of 6 groups in the place navigation test during 7 test days also showed significant differences between groups in test day 1,2,5,and 7(P<0.05 or P<0.01).Conclusions:By intraperitioneal injection of MK-801 in adolescent rats may prepare MK-801-induced schizophrenia model successfully.D-serine can improve positive and negative symptoms,and also have effects on the working memory and learning functions in schizophrenia model rats. |
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