Comparative Effects of Acute and Chronic Administration of Amphetamine on Local Cerebral Glucose Utilization in the Conscious Rat
Comparative Effects of Acute and Chronic Administration of Amphetamine on Local Cerebral Glucose Utilization in the Conscious Rat
复制标题
急性和慢性服用安非他明对清醒大鼠局部脑葡萄糖利用的影响比较
DOI：
10.1038/jcbfm.1983.22
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发表时间：
1983
影响因子：
6.3
通讯作者：
Louis Sokoloff
中科院分区：
文献类型：
--
作者：
F. Orzi;Diana Dow;J. Jehle;Charles Kennedy;Charles Kennedy;Louis Sokoloff
采用2-脱氧葡萄糖法对急性或慢性给予d-苯丙胺的大鼠进行研究。通过单次静脉内和/或每日重复腹膜内注射或通过皮下植入的渗透泵给予药物。每种给药方式都会产生特定的代谢效应。急性剂量的d-安非他明，5毫克/公斤，刺激葡萄糖利用的一些大脑结构，特别是锥体外系运动系统的组成部分。在中脑边缘多巴胺能系统的组分中未观察到影响。每日重复给药5 mg/kg，持续2周，除非剂量在3周内逐渐增加至15 mg/kg的毒性水平，否则无影响。然而，通过渗透泵维持的剂量（12-15 mg/kg/天，持续1周或6-7 mg/kg/天，持续2周）导致中脑边缘系统的重要组成部分-葡萄糖利用率的选择性增加。这一发现可能对安非他明精神病的机制具有重要意义，安非他明精神病有时被认为是精神分裂症的模型，并被认为是支持该疾病的多巴胺假说的证据。
The 2-deoxyglucose method was employed in rats following either acute or chronic administration of d-amphetamine. The drug was given either by a single intravenous and/or repeated daily intraperitoneal injections or by osmotic pumps implanted subcutaneously. Each mode of administration resulted in a specific constellation of metabolic effects. Acute doses of d-amphetamine, 5 mg/kg, stimulated glucose utilization in a number of cerebral structures, particularly the components of the extrapyramidal motor system. No effects were observed in components of the mesolimbic dopaminergic system. Repeated daily doses of 5 mg/kg for 2 weeks had no effects unless the dosage was progressively increased to toxic levels of 15 mg/kg over a 3-week period. Dosage sustained by osmotic pumps (12–15 mg/kg/day for 1 week or 6–7 mg/kg/day for 2 weeks), however, resulted in a selected increase in glucose utilization in the accumbens, an important component of the mesolimbic system. This finding may be of significance to the mechanism of amphetamine psychosis, which is sometimes regarded as a model of schizophrenia and is considered to be evidence in support of the dopamine hypothesis of the disease.