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目的研究新型毒品氯胺酮长期低剂量应用对食蟹猴行为学、海马和前额皮质超微结构的影响。方法 12只食蟹猴随机分为氯胺酮组(8只)和对照组(4只)。氯胺酮组每日静脉注射氯胺酮(1mg/kg),对照组每日静脉注射生理盐水(1mL/kg),定期对12只猴进行行为学分析,6个月后处死取材,透射电镜下观察海马及前额皮质超微结构的变化。结果与对照组相比,氯胺酮组运动行为无统计学意义(P﹥0.05);海马区出现神经细胞坏死,胶质细胞凋亡及大量脂褐素堆积;前额皮质区呈现大量自噬体,粗面内质网数量明显减少,神经元坏死和胶质细胞凋亡,而对照组两区域电镜超微结构正常。结论氯胺酮低剂量长期应用可导致海马及前额皮质超微结构的变化,主要表现为神经细胞的变性、坏死和凋亡,这一变化较行为学变化更为敏感。
Objective To investigate the effects of long-term, low-dose ketamine on behavior, hippocampus and prefrontal cortex ultrastructure in cynomolgus monkeys. Methods 12 cynomolgus monkeys were randomly divided into ketamine group (n = 8) and control group (n = 4). Ketamine group was injected with ketamine (1mg / kg) daily. In the control group, normal saline (1mL / kg) was intravenously injected into the control group. Twelve monkeys were subjected to behavioral analysis on a regular basis. After 6 months, the rats were sacrificed and the hippocampus Changes in the ultrastructure of the prefrontal cortex. Results Compared with the control group, the kinetics of ketamine group was not statistically significant (P> 0.05). Neuronal cell death, glial cell apoptosis and accumulation of lipofuscin appeared in the hippocampus. The prefrontal cortex presented a large number of autophagosomes The number of endoplasmic reticulum was significantly reduced, neuronal necrosis and glial cell apoptosis, while the control group two regions electron microscopy ultrastructure normal. Conclusion Long-term administration of ketamine at low dose can lead to changes in the ultrastructure of the hippocampus and prefrontal cortex, which is mainly manifested as degeneration, necrosis and apoptosis of nerve cells. This change is more sensitive than behavioral changes.