Effects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum
Effects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum
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DOI：
10.1016/j.ejphar.2014.02.012
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发表时间：
2014-04-15
影响因子：
5
通讯作者：
Matsuda, Toshio
中科院分区：
文献类型：
--
作者：
Higashino, Kosuke;Ago, Yukio;Matsuda, Toshio
前额叶儿茶酚胺神经传递在注意力缺陷/多动障碍（ADHD）药物的治疗作用中发挥着关键作用。我们最近表明，血清素/去甲肾上腺素再摄取抑制剂和去甲肾上腺素再摄取抑制剂地昔帕明可减轻自发性高血压大鼠（ADHD 动物模型）的水平过度活跃，并且这些药物是 ADHD 的潜在药物治疗剂。在本研究中，我们使用体内微透析来研究急性和慢性（每天一次，持续 3 周）给予血清素/去甲肾上腺素再摄取抑制剂文拉法辛和去甲肾上腺素再摄取抑制剂地昔帕明对去甲肾上腺素、多巴胺和血清素水平的影响，以及小鼠前额叶中神经元活动标记物 c-Fos 表达的影响。 皮质和纹状体。急性和慢性文拉法辛给药均增加前额去甲肾上腺素、多巴胺和血清素水平以及纹状体去甲肾上腺素和血清素水平。急性和慢性服用地昔帕明都会增加前额去甲肾上腺素和多巴胺水平以及纹状体去甲肾上腺素水平，慢性服用产生更强烈的增加。慢性地昔帕明不影响纹状体多巴胺和血清素水平。急性和慢性文拉法辛施用均增加了前额皮质中c-Fos的表达，而慢性而非急性地昔帕明施用增加了前额皮质中c-Fos III的表达。急性和慢性文拉法辛给药都在一定程度上增加了纹状体c-Fos的表达，而地昔帕明给药则没有。这些结果表明，急性和慢性文拉法辛和慢性地昔帕明给药最大限度地激活前额肾上腺素能和多巴胺能系统，而不影响小鼠的纹状体多巴胺能系统。 (C) 2014 Elsevier B.V. 保留所有权利。
Prefrontal catecholamine neurotransmission plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). We have recently shown that serotonin/noradrenaline reuptake inhibitors and the noradrenaline reuptake inhibitor desipramine attenuated horizontal hyperactivity in spontaneously hypertensive rats, an animal model of ADHD, and that these drugs are potential pharmacotherapeutics for ADHD. In this study, we used in vivo microdialysis to study the effects of acute and chronic (once daily for 3 weeks) administration of the serotonin/noradrenaline reuptake inhibitor venlafaxine and the noradrenaline reuptake inhibitor desipramine on noradrenaline, dopamine, and serotonin levels, and the expression of the neuronal activity marker c-Fos in the mouse prefrontal cortex and striatum. Both acute and chronic venlafaxine administration increased prefrontal noradrenaline, dopamine, and serotonin levels and striatal noradrenaline and serotonin levels. Both acute and chronic desipramine administration increased prefrontal noradrenaline and dopamine levels and striatal noradrenaline levels, with chronic administration yielding stronger increase. Chronic desipramine did not affect striatal dopamine and serotonin levels. Both acute and chronic venlafaxine administration increased the expression of c-Fos in the prefrontal cortex, whereas chronic, but not acute, desipramine administration increased the expression of c-Fos Ill the prefrontal cortex. Both acute and chronic venlafaxine administration increased the striatal c-Fos expression to some degree, whereas desipramine administration did not. These results suggest that acute and chronic venlafaxine and chronic desipramine administration maximally activate the prefrontal adrenergic and dopaminergic systems without affecting striatal dopaminergic systems in mice. (C) 2014 Elsevier B.V. All rights reserved.