多巴胺激动剂阿朴吗啡对东莨菪碱诱导小鼠学习记忆障碍的影响

目的：研究多巴胺（DA）对小鼠学习记忆障碍的影响及其机制。方法：实验1采用腹腔注射东莨菪碱0．3mg／kg（SCOP 0．3，n=10）和3．0mg／kg（SCOP3．0），连续注射60d，在第53天和60天用避暗法测定记忆行为，第60天处死动物后取脑用免疫组化的方法测定TH-ir和Fos-ir的表达。实验2根据实验1结果造小鼠记忆障碍的模型后将小鼠分成4组，1组腹腔注射生理盐水（NS），其他3组腹腔注射阿朴吗啡0．1mg/kg（APO 0．1）、0．5mg／kg（APO 0．5）和2．0mg／kg（APO 2．0），每组10只动物，连续30d。在注射阿朴吗啡第23天和30天测定避暗行为。第30天处死动物后取脑用免疫组化的方法测定Fos-ir和TH-ir的表达。结果：避暗法测定记忆发现东莨菪碱抑制小鼠的记忆。第60天，东莨菪碱3．0mg／kg组（SCOP3．0）的潜伏期比NS组显著缩短，仅是NS组的1／4（P〉0．05），错误次数比Ns组增加了大约4倍（P〉0．05），SCOP 0．3组的潜伏期和错误次数与NS组没有明显差异。免疫组化结果表明在伏隔核和海马区的CAl和CA3的Fos-ir细胞数明显降低（P〈0．01），且被盖腹侧区的酪氨酸羟化酶（TH-ir）和共表达TH／Fos-ir细胞显著减少（P〈0．01）。注射阿朴吗啡后明显缓解了小鼠的记忆障碍，且腹侧被盖区TH-ir细胞增加（P〈0．05）。结论：阿朴吗啡明显减轻东莨菪碱诱导的小鼠记忆障碍，是通过增强腹侧被盖区多巴胺神经元的活性来实现的。

Effect of dopamine receptor agonist apomorphine on scopolamine induced memory deficits in mice

Objective： To research the mechanism of dopamine （DA） controlled memory in mice. Methods： Mice received i.p. injection of scopolamine （0.3 mg/kg, SCOP 0.3, and 3.0mg/kg, SCOP 3.0, respectively, n = 10） and saline （NS, n = 10） for 60 days in experiment 1. Memory of mice was detected by dark avoidance behavior in the 53^rd d and the 60^th d. Animals were sacrificed after the memory test; brain tissues were processed for Fos-ir and TH-ir by immunohistochemistry. Mice were divided into four groups according results of expriment 1, they received i.p. injection of apomorphine （0.1mg/kg, APO 0.1, 0.5 mg/kg, APO 0.5, and 2.0 mg/kg, APO 2.0 respectively, n = 10）. Results： Memory was inhibited in mice injected scopolamine 3.0 mg/kg. Latency was signitlcanfly less than in NS group, only 1/ 4 that of NS group （ P 〉 0.05）. The number of mistake of SCOP 3.0 group increased about four times than that of NS group （P 〉 0.05）. But there was no difference of latency and number of mistake between SCOP 0.3 and NS group in expriment 1. Scopolamine-induced memory deficit was associated with decreased cellular activation, indicated by Fos immtmoreactive （ir） staining, in NAcc CA1 and CA3 （ P〈 0.05）, and also associated with decreases in the number of cells labeled for tyrosine hydroxylase （TH-ir）, the rate limiting enzyme for dopamine conversion（ P 〈 0.01 ） and the number of cells co-labeled for TH-ir/Fos-ir （ P 〈 0.01 ） in the ventral tegmental area（VTA）, apomorphine lessened scopolamine-induced memory deficit in experiment 2. The number of cells co-labeled for TH-ir/Fos-ir （ P 〈 0.05） was increased in VTA after apomorphine treatment. Conclusion： Apomorphine lessened scopolamine-induced memory deficit in mice by increasing DA activities in VTA.