Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Yerkes Imaging Center, 954 Gatewood Road, Atlanta, GA 30322-4250, USA.
Psychopharmacology (Berl). 2012 Apr;220(3):495-508. doi: 10.1007/s00213-011-2504-0. Epub 2011 Oct 13.
Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established.
In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed.
In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high-pressure liquid chromatography.
Exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance.
These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions.
大量证据表明，苯丙胺衍生物会耗尽大脑单胺能神经递质。然而，苯丙胺引起的神经化学耗竭对行为和认知的后果尚未得到很好的确定。
在这项研究中，研究人员使小鼠暴露于已知可耗尽多巴胺和血清素等单胺神经递质的 3,4-亚甲二氧基甲基苯丙胺（MDMA）、甲基苯丙胺（METH）或对氯苯丙胺（PCA）的给药方案中，并评估这些给药方案对学习和记忆的影响。
在相同的动物中，我们通过被动回避（PA）行为来确定学习和记忆的缺陷，并通过体外高压液相色谱法来确定纹状体、前额叶皮层、扣带回、海马体和杏仁核中单胺神经递质及其主要代谢物的组织含量变化。
暴露于 METH 和 PCA 会损害 PA 表现，并导致几个脑区的多巴胺、血清素及其代谢物明显减少。多元线性回归分析显示，前纹状体中的多巴胺组织浓度是 PA 表现的最强预测因子，扣带回中的血清素代谢物 5-羟吲哚乙酸的组织浓度也有显著贡献。与 METH 和 PCA 的作用相反，暴露于 MDMA 不会耗尽前纹状体中的多巴胺水平或扣带回中的 5-羟吲哚乙酸水平，也不会损害 PA 表现。
这些研究表明，某些苯丙胺会损害小鼠的 PA 表现，而这些损害可能归因于特定的神经化学耗竭。
