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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 effect of chronic alcoholism on spatial learning and memory, changes of opioid peptide in brain area and the therapeutic effect of naloxone, an opioid receptor antagonist. Methods: Three-week-old male Sprague-Dawley rats were divided into four groups: Rats in groups A and B were given free alcohol for 8 weeks from 6% to 15% (v / v) to establish a model of chronic alcoholism Groups C and D were given free access to drinking water. After 8 weeks, rats in groups B and D were injected intraperitoneally with naloxone for 10 days. Groups A and C were injected intraperitoneally with saline. Morris water maze training was then used to compare spatial learning and memory The content of β-endorphin (β-EP) and Dyn A: dynophine A in per gram tissue of hypothalamus, hippocampus, striatum and prefrontal cortex were determined by radioimmunoassay . Results: In the Morris water maze concealed platform training, the escape latency of group A was longer than that of control group C (P <0.01 or P <0.05) at multiple time points. In group B, Naloxone treatment was significantly shorter than that of group A (P <0.05). The levels of β-EP in the hypothalamus, hippocampus and striatum of rats after chronic alcohol intake increased to some extent (P <0.01 or P <0.05 or P <0.001) And Dyn A decreased in the prefrontal cortex. However, Naloxone treatment could partly or completely reverse the change of β-EP and Dyn A content in the brain and improve the learning and memory behaviors of rats (P < 0.05). CONCLUSION: Alcohol impaired the learning and memory abilities of rats, which may be related to the changes of β-EP and Dyn A levels in learning-relevant brain regions. Naloxone reversed the changes of opioid peptides in some brain regions, Learning and memory disorders have some improvement.