Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration of the antidepressant/antipanic drug phenelzine
Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration of the antidepressant/antipanic drug phenelzine
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DOI：
10.1016/s0006-2952(00)00244-6
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发表时间：
2000-05-15
影响因子：
5.8
通讯作者：
Baker, GB
中科院分区：
文献类型：
--
作者：
Parent, MB;Habib, MK;Baker, GB
苯elzine （PLZ）是一种非选择性单胺氧化酶（MAO）抑制剂，常用于治疗抑郁症和恐慌症。急性给药PLZ会产生几种神经化学变化，包括大脑中儿茶酚胺（去甲肾上腺素（NE）和多巴胺（DA））、5-羟色胺（5-HT）以及氨基酸丙氨酸和γ -氨基丁酸（GABA）水平的增加。本系列实验的目的是表征这些plz诱导的变化的时间过程。雄性Sprague-Dawley大鼠在急性PLZ给药后6、24、48、96、168或336小时被处死（15或30 mg/kg， i.p，基于游离基重量）。用高效液相色谱法测定全脑单胺和氨基酸水平，用放射化学方法测定MAO A和B活性。结果表明，PLZ在注射后6和24小时改变了氨基酸水平，但在48小时后没有改变。相比之下，PLZ对MAO活性和单胺的影响更为持久。例如，注射后1周观察到plz诱导的多巴胺和5-羟色胺增加，plz诱导的MAO活性抑制持续2周。因此，除了证明PLZ对MAO活性和单胺的影响是持久的外，这些结果还表明PLZ对MAO活性和单胺和氨基酸脑水平的影响是暂时游离的。这些关于PLZ对神经化学的长期影响的发现将对PLZ急性效应的行为研究的设计和解释具有相当重要的意义。(C) 2000 Elsevier Science Inc.；
Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commonly used to treat depression and panic disorder. Acute administration of PLZ produces several neurochemical changes, including an increase in brain levels of the catecholamines norepinephrine (NE) and dopamine (DA), of 5-hydroxytryptamine (5-HT), and of the amino acids alanine and gamma-aminobutyric acid (GABA). The goal of the present series of experiments was to characterize the time course of these PLZ-induced changes. Male Sprague-Dawley rats were sacrificed 6, 24, 48, 96, 168, or 336 hr after acute PLZ administration (15 or 30 mg/kg, i.p., based on free base weight). Whole brain levels of monoamines and amino acids were determined using HPLC, and MAO A and B activities were determined using a radiochemical procedure. The results indicated that PLZ changed amino acid levels 6 and 24 hr after injection, but not 48 hr later. In contrast, the effects of PLZ on MAO activity and monoamines were longer-lasting. For example, PLZ-induced increases in dopamine and 5-HT were observed 1 week after injection, and PLZ-induced inhibition of MAO activity persisted for 2 weeks. Thus, in addition to demonstrating that the effects of PLZ on MAO activity and monoamines were long-lasting, these results indicate that the effects of PLZ on MAO activity and on brain levels of monoamines and amino acids are temporally dissociated. These findings regarding the long-term effects of PLZ on neurochemistry will have considerable critical implications for the design and interpretation of behavioral studies of the acute effects of PLZ. (C) 2000 Elsevier Science Inc.