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化学遗传学激活中脑多巴胺神经元对大鼠五选择连续反应时任务中的注意力有影响,但对冲动性无影响。

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time Task in Rats.

作者信息

Boekhoudt Linde, Voets Elisa S, Flores-Dourojeanni Jacques P, Luijendijk Mieneke Cm, Vanderschuren Louk Jmj, Adan Roger Ah

机构信息

Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

Neuropsychopharmacology. 2017 May;42(6):1315-1325. doi: 10.1038/npp.2016.235. Epub 2016 Oct 17.

Abstract

Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats. We found that activation of DA neurons in both the VTA and SNc impaired attention by increasing trial omissions. In addition, SNc DA neuron activation decreased attentional accuracy. Surprisingly, enhanced DA neuron activity did not affect impulsive action in this task. These results show that enhanced midbrain DA neuronal activity induces deficits in attentional performance, but not impulsivity. Furthermore, DA neurons in the VTA and SNc have different roles in regulating attention. These findings contribute to our understanding of the neural substrates underlying attention deficits and impulsivity, and provide valuable insights to improve treatment of these symptoms.

摘要

注意力缺陷和过度冲动是精神疾病的关键特征,如注意力缺陷多动障碍、精神分裂症和成瘾。这些注意力表现和冲动行为的缺陷与异常的多巴胺(DA)信号传导有关,但这些缺陷是否源于中脑DA神经元活动增强仍不清楚。在这里,我们采用了一种新方法,通过测试化学遗传学激活腹侧被盖区(VTA)或黑质致密部(SNc)中的DA神经元对大鼠五选择连续反应时任务(5-CSRTT)中的注意力和冲动性的影响。我们发现,VTA和SNc中DA神经元的激活通过增加试验遗漏而损害注意力。此外,SNc中DA神经元的激活降低了注意力准确性。令人惊讶的是,增强的DA神经元活动在该任务中并未影响冲动行为。这些结果表明,中脑DA神经元活动增强会导致注意力表现缺陷,但不会导致冲动性。此外,VTA和SNc中的DA神经元在调节注意力方面具有不同作用。这些发现有助于我们理解注意力缺陷和冲动性的神经基础,并为改善这些症状的治疗提供有价值的见解。

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