海马齿状回区多巴胺D1受体在大鼠主动回避学习中的作用及其机制

doi:10.13481/j.1671-587x.20180605

摘要/Abstract

摘要： 目的：观察大鼠海马齿状回（DG）区的多巴胺（DA）水平在大鼠主动回避条件反射建立及消退过程中的变化，探讨D1受体在大鼠主动回避学习中的作用及其机制。方法：24只SD雄性成年大鼠随机分为非训练组、训练组、对照组和SCH组，每组6只。训练组大鼠每天进行穿梭箱训练，非训练组大鼠只放进穿梭箱而不进行训练，测定2组大鼠DG区细胞外液中DA水平。对照组和SCH组大鼠每天进行穿梭箱训练前向DG区注射生理盐水或SCH-23390，训练后测定2组大鼠DG区细胞外液中谷氨酸（Glu）水平和场兴奋性突触后电位（fEPSP）幅值。利用穿梭箱的行为学分析系统记录各组大鼠主动回避反应率，采用脑部微量透析法和高效液相色谱法测定各组大鼠DG区DA和Glu水平，采用电生理学记录法观察各组大鼠DG区fEPSP幅值。结果：训练组大鼠DG区DA水平在条件反射的建立过程中逐渐升高，且在消退过程中逐渐降低；与第1天比较，第5天大鼠DG区DA水平明显升高（P<0.05），非训练组大鼠DG区各个时间点DA水平比较差异无统计学意义（P>0.05）。对照组大鼠训练第5天达到主动回避条件反射建立标准（主动回避反应率>65%），第7天达到消退标准（主动回避反应率<35%）。与第1天比较，第5天大鼠DG区Glu水平和fEPSP幅值均明显升高（P<0.05）；SCH组大鼠在整个训练过程中均未达到条件反射建立标准，且DG区Glu水平和fEPSP幅值在训练过程中未出现明显变化（P>0.05）；与对照组比较，训练第5天时SCH组大鼠DG区Glu水平和fEPSP幅值均明显降低（P<0.05）。结论：大鼠海马DG区DA可通过激活D1受体促进主动回避学习，其作用可能与增加DG局部Glu水平和突触传递效应有关。

关键词: 海马齿状回, 多巴胺D1受体, 主动回避学习, 长时程增强, 谷氨酸

Abstract: Objective: To observe the changes of dopamine (DA) levels in the hippocampal dentate gyrus (DG) region of the rats during the establishment and extinction process of active avoidance conditioned reflex, and to investigate the effect of D1 receptor in the active avoidance learning of the rats and its mechanism.Methods: A total of 24 male SD rats were randomly divided into non-training group, training group, control group and SCH group (n=6). The rats in training group were trained for active avoidance whereas the rats in non-training group were only put into the shuttle box without training, and then the DA levels in extracellular fluid in DG region of the rats in two groups were measured. In control and SCH groups, the saline or SCH-23390 was injected into the DG region of the rats before the active avoidance training, and then the glutamate (Glu) levels and the field excitatory postsynaptic potential (fEPSP) amplitudes in extracellular fluid in DG region of the rats in two groups were examined. The rates of active avoidance of the rats were recorded by behavioral analysis system of the shuttle box. The levels of DA and Glu in DG region of the rats were measured by microdialysis and HPLC techniques, and the amplitude of fEPSP in DG region of the rats was examined by electrophysiological recording.Results: The DA level in DG region of the rats in training group was gradually increased during the establishment process and was gradually decreased during the extinction process of conditioned reflex; compared with the 1st day, the DA level in DG region of the rats on the 5th day was markedly increased (P<0.05); the DA level in DG region of the rats in non-training group did not significantly change at different time points during the experimental process (P>0.05). In control group, the rats reached the establishment criterion on the 5th day (active avoidance rate >65%) and reached the criterion of extinction on the 7th day (active avoidance rate <35%); compared with the 1st day, the Glu level and fEPSP amplitude in DG region of the rats on the 5th day were significantly increased (P<0.05). In SCH group, the rats did not acquire the conditioned reflex, and the Glu level and fEPSP amplitude in DG region of the rats were not significantly changed during the whole behavioral training process (P>0.05). Compared with control group, the Glu level and fEPSP amplitude of the rats in SCH group on the 5th day were markedly decreased (P<0.05).Conclusion: DA in hippocampal DG region of the rats can facilitate the active avoidance learning via activation of D1 receptors, and its mechanism is associated with the enhancement of Glu level and synaptic transmission efficiency.

Key words: hippocampal dentate gyrus, dopamine D1 receptor, active avoidance learning, long-term potentiation, glutamate

中图分类号:

Q427

王玮瑶, 张岩, 赵可, 孙传博, 金清华. 海马齿状回区多巴胺D1受体在大鼠主动回避学习中的作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1138-1143.

WANG Weiyao, ZHANG Yan, ZHAO Ke, SUN Chuanbo, JIN Qinghua. Effect of dopamine D1 receptor in hippocampal DG region in active avoidance learning in rats and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1138-1143.

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