Metabolic mapping of the effects of intravenous methamphetamine administration in freely moving rats
Metabolic mapping of the effects of intravenous methamphetamine administration in freely moving rats
复制标题
静脉注射甲基苯丙胺对自由活动大鼠影响的代谢图谱
作者：
F. Pontieri;A. Crane;L. Seiden;M. Kleven;L. Porrino
用2-[14 C]脱氧葡萄糖法观察了急性静脉注射甲基苯丙胺（0.5- 2.5mg/kg）对自由活动大鼠局部脑葡萄糖利用率的影响。这些影响与甲基苯丙胺对同一动物同时评估的自发活动的影响相关。甲基苯丙胺给药导致锥体外系运动系统结构内葡萄糖利用率普遍呈剂量依赖性增加。葡萄糖利用率与苍白球、网状黑质、脚内核、丘脑底核和小脑外侧皮质的自发活动呈正相关。相比之下，在边缘系统内，代谢活动的变化较小，更具选择性。葡萄糖利用率增加，在所有剂量的测试，但在腹侧被盖区，杏仁核，前扣带回的葡萄糖利用率的变化，观察到只有在最高剂量的甲基苯丙胺测试。在黑质、中缝核和中缝背核中也发现了葡萄糖代谢率的显著增加。多巴胺和5-羟色胺在这些区域耗尽，以及在腹侧被盖区，其中葡萄糖利用率也增加，高剂量的甲基苯丙胺慢性治疗后。葡萄糖利用率的这些变化可能表明甲基苯丙胺的神经毒性作用所涉及的生化过程中的干扰。
The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of methamphetamine (0.5–2.5 mg/kg) on rates of local cerebral glucose utilization in freely-moving rats. These effects were correlated with the effects of methamphetamine on locomotor activity assessed simultaneously in the same animals. Methamphetamine administration resulted in widespread dose-dependent increases in glucose utilization within structures of the extrapyramidal motor system. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, entopeduncular nucleus, subthalamic nucleus, and the lateral cerebellar cortex. In contrast, within the limbic system alterations in metabolic activity were smaller and more selective. Glucose utilization was increased in the nucleus accumbens at all doses tested, but alterations in glucose utilization in the ventral tegmental area, amygdala, and anterior cingulate were observed only at the highest doses of methamphetamine tested. Significant increases in rates of glucose metabolism were also found in the substantia nigra compacta and in the median and dorsal raphe nuclei. Dopamine and serotonin are depleted in these regions, as well as in the ventral tegmental area where glucose utilization was also increased, following chronic treatment with high doses of methamphetamine. These changes in glucose utilization may be indicative of disturbances in the biochemical processes involved in the neurotoxic effects of methamphetamine.