Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, México City 14269, Mexico.
Behav Brain Res. 2010 Jul 29;211(1):132-9. doi: 10.1016/j.bbr.2010.03.023. Epub 2010 Mar 20.
This study is an attempt to demonstrate whether bupropion (BP) and diethylpropion (DEP) exert their pharmacological actions by similar neurochemical mechanisms in the dorsal striatum. In this regard, the release of dopamine (DA), glutamate (Glu), and GABA, was determined in the rat dorsal striatum after acute (5 min) and chronic (15 consecutive days) treatments, and subsequently correlated with the locomotor activities produced by these drugs. The results from the acute experiments indicate that BP and DEP (40 mg/kg) increase locomotor activity, whereas chronic DEP treatment decreases locomotor activity by unspecific mechanisms. Acute BP treatment produces significant DA and Glu, but not GABA, releases. A lesser extent of DA release and tissue content of DA and its metabolites, and consequently less locomotor activity, was observed after chronic BP treatment. Acute DEP (5mg/kg) was only able to slightly increase DA release and to decrease the tissue levels of DA, but no other markers, with practically nil locomotor activity, whereas chronic DEP produced even less neurotransmitter release. The observed difference between BP and DEP might be based on that although both drugs inhibit the DA and norepinephrine transporters, the BP-induced nicotinic receptor inhibition has yet to be demonstrated for DEP.
这项研究旨在探讨安非他酮(BP)和右苯丙胺(DEP)是否通过相似的神经化学机制在背侧纹状体发挥其药理作用。在这方面,在急性(5 分钟)和慢性(连续 15 天)治疗后,测定了大鼠背侧纹状体中多巴胺(DA)、谷氨酸(Glu)和 GABA 的释放,并与这些药物产生的运动活性相关联。急性实验结果表明,BP 和 DEP(40mg/kg)增加运动活性,而慢性 DEP 治疗通过非特异性机制降低运动活性。BP 治疗后会引起明显的 DA 和 Glu 释放,但不会引起 GABA 释放。慢性 BP 治疗后,DA 释放和 DA 及其代谢物的组织含量减少,因此运动活性降低。急性 DEP(5mg/kg)仅能轻微增加 DA 释放并降低 DA 的组织水平,但运动活性几乎为零,其他标志物也没有变化,而慢性 DEP 则导致更少的神经递质释放。BP 和 DEP 之间的观察到的差异可能基于这样的事实,尽管这两种药物都抑制了 DA 和去甲肾上腺素转运体,但尚未证明 DEP 会引起 BP 诱导的烟碱受体抑制。