纳洛酮对慢性酒精中毒学习记忆障碍大鼠脑内阿片肽含量的影响

Naloxone effects on opioid peptides level in brain regions of learning and memory impairment induced by chronic ethanol in rats

目的:研究慢性酒精中毒对大鼠空间学习记忆的影响、脑区内阿片肽含量的变化,及其阿片受体拮抗剂纳洛酮的治疗作用。方法:3周龄雄性SD大鼠分为4组:给A、B组大鼠自由饮用由含6%逐渐递增至15%(v/v)的乙醇水溶液8周,建立慢性酒精中毒模型,而C、D组自由饮水;8周后B、D大鼠连续10天腹腔注射纳洛酮,A、C组腹腔注射生理盐水;然后用Morris水迷宫训练方法,比较四组大鼠的空间学习记忆能力的差异;采用放射免疫法测定下丘脑、海马、纹状体和前额皮质每克组织中β内啡肽(β-EP:β endorphin)和强啡肽A(Dyn A:dynophine A)的含量。结果:在Morris水迷宫隐匿平台训练中,有多个时段A组动物的逃避潜伏期较正常对照组C长(P<0.01或P<0.05),其中纳洛酮治疗后B组比A组明显缩短(P<0.05)。大鼠慢性酒精摄入后下丘脑、海马和纹状体内的β-EP水平较正常对照组出现不同程度的升高(P<0.01或P<0.05或P<0.001),而海马、纹状体和前额皮质内的Dyn A水平却出现下降;而给予纳洛酮处理后,能部分或完全逆转脑区内β-EP和Dyn A含量的变化并改善大鼠学习记忆的行为学成绩(P<0.05)。结论:酒精损害了大鼠的学习记忆能力,其机制可能与学习相关脑区内的β-EP和Dyn A水平的变化有关;纳洛酮逆转其部分脑区内阿片肽水平的变化,从而对学习记忆障碍有一定的改善作用。

Objective： To study the effects of chronic ethanol intake（CEI） on spatial learning and memory and the content of opioid peptide in the brain regions in rats. Methods： 40 male rats, aged 3 weeks, were divided into four groups. Alcohol-induced learning and memory impairment model （Group A and B ） was established by ingesting solution of ethanol from a 6% to 15% for 8 weeks while group C and D drank water freely. After that, group B and D received naloxone injection （i.p.） for 10 days while group A and C were treated with the same volume saline injection. Spatial learning and memory abilities were evaluated with escape latency to find a hidden platform in Morris Water Maze. The content of β-EP and Dyn A in the brain regions such as hypothalamus, hippocampus, striatum and prefrontal cortex were determined by radioimmunity method. Results： The level of β-EP and Dyn A in the several brain regions of CEI in rats increased or decreased compared with that of the control group respectively （P〈0.01 or P〈0.05 or P〈0.001）, which is parallel to the ethanol deleterious effect on the spatial learning and memory. Naloxone can fully or partly reversed the change of the opioid peptide level and improve spatial learning and memory of the model animals （P〈0.05）. Conclusions： The mechanism of learning and memory impairment caused by CEI may be related to the alteration of the opioid peptide release and their activity in the brain regions.