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中脑皮质多巴胺能系统无法解释注意力缺陷多动障碍(ADHD)动物模型——自发性高血压大鼠(SHR)中的多动现象。

The mesocortical dopaminergic system cannot explain hyperactivity in an animal model of attention deficit hyperactivity disorder (ADHD)- Spontaneously hypertensive rats (SHR).

作者信息

Gungor Aydin Aysegul, Adiguzel Esat

机构信息

Department of Psychology, Rutgers University-New Brunswick, Piscataway, NJ, 08854, USA.

Department of Anatomy, Faculty of Medicine, Pamukkale University, 20070, Denizli, Turkey.

出版信息

Lab Anim Res. 2023 Sep 14;39(1):20. doi: 10.1186/s42826-023-00172-5.

Abstract

BACKGROUND

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders with morphological brain abnormalities. There is a growing body of evidence that abnormalities in the dopaminergic system may account for ADHD pathogenesis. However, it is not clear whether the dopaminergic system is hyper or hypoactive. To determine whether the DA neurons and/or axons deficiency might be the cause of the postulated dopaminergic hypofunction in spontaneously hypertensive rats (SHR, animal model of ADHD), this study examined the dopaminergic neurons and fibers in the brain tissues of SHRs and Wistar Kyoto rats (WKY, control animals). Here, we performed immunohistochemical tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) staining on brain sections collected on juveniles from SHR and WKY. Moreover, behavioral testing to examine the hyperactivity in the open field area was also elucidated.

RESULTS

The mesocortical dopaminergic system appears to be normal in juvenile SHR, as suggested by (i) no alteration in the area density of TH-immunoreactive (TH-ir) dopaminergic neurons in the ventral tegmental area (VTA), (ii) no alterations in the volume density of TH-ir fibers in layer I of the prelimbic (PrL) subregion of medial PFC (mPFC), (iii) no alteration in the percentage of TH-ir dopaminergic fibers in layer I of the PrL subregion of mPFC as revealed by TH and/or DBH immunoreactivity. Furthermore, the SHR showed increased locomotor activity than WKY in the open field test.

CONCLUSIONS

The demonstration of no alteration in mesocortical dopaminergic neurons and fiber in SHR raises some concern about the position of SHR as an animal model of the inattentive subtype of ADHD. However, these results strengthen this strain as an animal model of hyperactive/impulsive subtype ADHD for future studies that may elucidate the underlying mechanism mediating hyperactivity and test various treatment strategies.

摘要

背景

注意缺陷多动障碍(ADHD)是最常见的伴有脑形态异常的神经精神疾病之一。越来越多的证据表明,多巴胺能系统异常可能是ADHD发病机制的原因。然而,尚不清楚多巴胺能系统是功能亢进还是功能减退。为了确定多巴胺能神经元和/或轴突缺乏是否可能是自发性高血压大鼠(SHR,ADHD动物模型)中假定的多巴胺能功能减退的原因,本研究检查了SHR和Wistar Kyoto大鼠(WKY,对照动物)脑组织中的多巴胺能神经元和纤维。在此,我们对从SHR和WKY的幼体收集的脑切片进行了免疫组织化学酪氨酸羟化酶(TH)和多巴胺-β-羟化酶(DBH)染色。此外,还进行了行为测试以检查旷场区域的多动情况。

结果

(i)腹侧被盖区(VTA)中TH免疫反应性(TH-ir)多巴胺能神经元的面积密度无变化,(ii)内侧前额叶皮质(mPFC)前边缘(PrL)亚区I层中TH-ir纤维的体积密度无变化,(iii)通过TH和/或DBH免疫反应性显示,mPFC的PrL亚区I层中TH-ir多巴胺能纤维的百分比无变化,这表明幼年SHR的中皮质多巴胺能系统似乎正常。此外,在旷场试验中,SHR的运动活性比WKY增加。

结论

SHR中脑皮质多巴胺能神经元和纤维无变化的证明引发了对SHR作为注意力不集中型ADHD动物模型地位的一些担忧。然而,这些结果加强了该品系作为多动/冲动型ADHD动物模型的地位,以便未来的研究可以阐明介导多动的潜在机制并测试各种治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca47/10500870/8065e1ac3e0a/42826_2023_172_Fig1_HTML.jpg

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