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嗅结节各亚区域中细胞外多巴胺的异质性调节

Heterogeneous extracellular dopamine regulation in the subregions of the olfactory tubercle.

作者信息

Park Jinwoo, Wakabayashi Ken T, Szalkowski Caitlin, Bhimani Rohan V

机构信息

Department of Biotechnical and Clinical Laboratory Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

出版信息

J Neurochem. 2017 Aug;142(3):365-377. doi: 10.1111/jnc.14069. Epub 2017 Jun 20.

Abstract

Recent studies show that dense dopamine (DA) innervation from the ventral tegmental area to the olfactory tubercle (OT) may play an important role in processing multisensory information pertaining to arousal and reward, yet little is known about DA regulation in the OT. This is mainly due to the anatomical limitations of conventional methods of determining DA dynamics in small heterogeneous OT subregions located in the ventral most part of the brain. Additionally, there is increasing awareness that anteromedial and anterolateral subregions of the OT have distinct functional roles in natural and psychostimulant drug reinforcement as well as in regulating other types of behavioral responses, such as aversion. Here, we compared extracellular DA regulation (release and clearance) in three subregions (anteromedial, anterolateral, and posterior) of the OT of urethane-anesthetized rats, using in vivo fast-scan cyclic voltammetry following electrical stimulation of ventral tegmental area dopaminergic cell bodies. The neurochemical, anatomical, and pharmacological evidence confirmed that the major electrically evoked catecholamine in the OT was DA across both its anteroposterior and mediolateral extent. While both D2 autoreceptors and DA transporters play important roles in regulating DA evoked in OT subregions, DA in the anterolateral OT was regulated less by the D2 receptors when compared to other OT subregions. Comparing previous data from other DA rich ventral striatum regions, the slow DA clearance across the OT subregions may lead to a high extracellular DA concentration and contribute towards volume transmission. These differences in DA regulation in the terminals of OT subregions and other limbic structures will help us understand the neural regulatory mechanisms of DA in the OT, which may elucidate its distinct functional contribution in the ventral striatum towards mediating aversion, reward and addiction processes.

摘要

最近的研究表明,从腹侧被盖区到嗅结节(OT)的密集多巴胺(DA)神经支配可能在处理与唤醒和奖赏相关的多感官信息中发挥重要作用,但对OT中DA的调节知之甚少。这主要是由于传统方法在确定位于大脑最腹侧的小异质性OT亚区域中DA动态时存在解剖学限制。此外,人们越来越意识到,OT的前内侧和前外侧亚区域在天然和精神兴奋剂药物强化以及调节其他类型的行为反应(如厌恶)中具有不同的功能作用。在这里,我们使用在体快速扫描循环伏安法,在电刺激腹侧被盖区多巴胺能细胞体后,比较了乌拉坦麻醉大鼠OT的三个亚区域(前内侧、前外侧和后部)的细胞外DA调节(释放和清除)。神经化学、解剖学和药理学证据证实,OT中主要的电诱发儿茶酚胺在其前后和中外侧范围内均为DA。虽然D2自身受体和DA转运体在调节OT亚区域诱发的DA中都起重要作用,但与其他OT亚区域相比,前外侧OT中的DA受D2受体的调节较少。与其他富含DA的腹侧纹状体区域的先前数据相比,OT亚区域中缓慢的DA清除可能导致细胞外DA浓度升高,并有助于容积传递。OT亚区域和其他边缘结构终末中DA调节的这些差异将有助于我们理解OT中DA的神经调节机制,这可能阐明其在腹侧纹状体中对介导厌恶、奖赏和成瘾过程的独特功能贡献。

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