"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways

Jie Ding; Yiyun Ding; Jingjing Wu; Jialin Deng; Qingyang Yu; Junhong Wang

doi:10.1155/2022/9139841

"Jing-Ning Granules" Can Alleviate Attention Deficit Hyperactivity Disorder in Rats by Modulating Dopaminergic D2/D1-Like Receptor-Mediated Signaling Pathways

Evid Based Complement Alternat Med. 2022 Oct 28:2022:9139841. doi: 10.1155/2022/9139841. eCollection 2022.

Authors

Jie Ding^#¹, Yiyun Ding^#^{1

2}, Jingjing Wu³, Jialin Deng⁴, Qingyang Yu⁵, Junhong Wang¹

Affiliations

¹ Department of Pediatrics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
² School of Psychology, Capital Normal University, Beijing 100048, China.
³ Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China.
⁴ Department of Pediatrics, Beijing Huaxin Hospital, The First Affiliated Hospital of Tsinghua University, Beijing 100016, China.
⁵ Department of TCM, Children's Hospital of Chongqing Medical University, Chongqing 400016, China.

^# Contributed equally.

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear.

Objective: In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways.

Materials and methods: Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca²⁺ in the striatum was analyzed by a calcium kit.

Results: Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca²⁺/CAM/CAMKII signaling pathways.

Conclusion: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca²⁺/CaM/CaMKII signaling pathways.