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背景:中枢内催产素可作为一种神经递质或调质参与学习记忆、性行为、痛觉调节以及阿片耐受与依赖,海马内催产素能系统与阿片系统具有一定的相互作用。目的:探讨侧脑室注射催产素对大鼠脑左背侧海马CA1区神经元诱发放电的影响以及催产素与阿片受体之间可能的相互作用。设计:随机对照实验。单位:广东医学院生理教研室,武汉大学医学院生理系,武汉大学医学院病理学教研室。材料:实验于2002-09/2003-09在武汉大学医学院生理系完成,选用雄性SD大鼠36只。随机分为6组,生理盐水对照组、催产素处理组(0.2,2,20mg/L)、催产素受体拮抗剂+催产素(2mg/L)组、纳洛酮+催产素(2mg/L)组,每组6只。方法:脑海马CA1区细胞外记录采用玻璃微电极记录:用微电极推进器将电极插入脑海马CA1区。神经元放电经微电极放大器放大后,显示在示波器上进行观察。记录到神经元放电后,经双极不锈钢电极每隔5min刺激坐骨神经1次,共刺激50min10次。催产素0.2,2,20mg/L处理组通过侧脑室给药管匀速而缓慢注入催产素0.2,2,20mg/L5μL。催产素受体拮抗剂+催产素(2mg/L)组:侧脑室预先注射80mg/L催产素受体拮抗剂2.5μL,然后再注射2mg/L催产素2.5μL。纳洛酮+催产素(2mg/L)组:侧脑室预先注射400mg/L纳洛酮2.5μL,然后再注射2mg/L催产素2.5μL。以放电频率变化率为观察指标,检测不同剂量催产素对海马CA1区神经元诱发放电的影响及催产素受体拮抗剂、纳洛酮对催产素的作用。主要观察指标:各组大鼠刺激前后脑海马CA1区神经元诱发放电频率的变化率。结果:36只大鼠均进入结果分析。①侧脑室分别注射0.2,2,20mg/L催产素5μL使海马CA1神经元诱发放电频率明显降低,剂量依赖关系明显。②催产素(2mg/L)对CA1神经元诱发放电的抑制作用可被侧脑室预先注射催产素受体拮抗剂(80mg/L,2.5μL)所阻断。③侧脑室注射纳洛酮(400mg/L,2.5μL)可明显减弱催产素(2mg/L)的作用。结论:催产素通过激活催产素受体可抑制海马CA1神经元对外周传入电信号的反应,中枢内阿片系统也参与催产素的抑制作用,当用纳洛酮阻断阿片受体后,催产素的抑制作用明显减弱。
BACKGROUND: Central oxytocin can serve as a neurotransmitter or modulate the learning and memory, sexual behavior, pain regulation and opiate tolerance and dependence. The oxytocin energy system in the hippocampus interacts with the opioid system. Objective: To investigate the effects of intracerebroventricular injection of oxytocin on the neuronal evoked discharge in hippocampal CA1 region of left dorsal horn of rats and the possible interaction between oxytocin and opioid receptor. Design: Randomized controlled experiment. Unit: Department of Physiology, Guangdong Medical College, Department of Physiology, Wuhan University School of Medicine, Department of Pathology, Wuhan University School of Medicine. MATERIALS: The experiment was performed in the Department of Physiology, Wuhan University Medical College from September 2002 to September 2003 with 36 male SD rats. The rats were randomly divided into 6 groups: saline control group, oxytocin treatment group (0.2,2,20mg / L), oxytocin receptor antagonist + oxytocin group (2mg / L), naloxone + oxytocin L) group, 6 in each group. METHODS: Extracellular recordings of hippocampal CA1 region were recorded using a glass microelectrode: the electrodes were inserted into the hippocampal CA1 region using a micro-electrode propeller. The neuron discharge is amplified by the microelectrode amplifier and displayed on the oscilloscope for observation. After the neurons were recorded and discharged, the sciatic nerve was stimulated once every 5 minutes by a bipolar stainless steel electrode, and co-stimulated for 10 times 10 times. Oxytocin 0.2,2,20 mg / L treatment group through the lateral ventricular administration tube slowly and slowly injected oxytocin 0.2,2,20 mg / L5μL. Oxytocin receptor antagonist + oxytocin (2 mg / L) group: The lateral ventricle was preinjected with 2.5 μL of 80 mg / L oxytocin receptor antagonist and then 2.5 μL of 2 mg / L oxytocin. Naloxone + oxytocin (2mg / L) group: Intracerebroventricular injection of 400mg / L naloxone 2.5μL, and then injected 2mg / L oxytocin 2.5μL. The effect of oxytocin on the neuronal evoked discharge in hippocampal CA1 region and the effects of oxytocin receptor antagonist and naloxone on oxytocin were observed by the rate of change of discharge frequency. MAIN OUTCOME MEASURES: The change rate of the firing frequency of neurons in CA1 area of hippocampus before and after stimulation in each group. Results: All 36 rats were involved in the result analysis. ① The lateral ventricle were injected with 0.2, 2, 20mg / L oxytocin 5μL of hippocampal CA1 neurons induced discharge frequency was significantly reduced, the dose-dependent relationship. ② The inhibitory effect of oxytocin (2mg / L) on CA1 neuron-induced discharge can be blocked by pre-injection of oxytocin receptor antagonist (80mg / L, 2.5μL) into lateral ventricle. ③ Intracerebroventricular injection of naloxone (400mg / L, 2.5μL) can significantly reduce the role of oxytocin (2mg / L). CONCLUSION: Oxytocin can inhibit the response of hippocampal CA1 neurons to peripheral electrical signals by activating oxytocin receptors. The central opioid system is also involved in the inhibitory effect of oxytocin. When naloxone blocks opioid receptors, oxytocin Su inhibitory effect was significantly weakened.