Bouchatta Otmane, Manouze Houria, Ba-M'Hamed Saadia, Landry Marc, Bennis Mohamed
Laboratory of Pharmacology, Neurobiology and Behavior, Faculty of Sciences, Cadi Ayyad University, Marrakesh, Morocco.
University of Bordeaux, Bordeaux, France.
Front Behav Neurosci. 2020 Feb 26;14:27. doi: 10.3389/fnbeh.2020.00027. eCollection 2020.
Attention-deficit/hyperactivity disorder (ADHD) is a syndrome characterized by impaired attention, impulsivity and hyperactivity in children. These symptoms are often maintained in adults. During adolescence, prefrontal cortex develops connectivity with other brain regions to engage executive functions such as, latent inhibition, attention and inhibitory control. In our previous work, we demonstrated the validity of the neonatal 6-Hydroxydopamine (6-OHDA) mouse model, a classical neurodevelopmental model mimicking major symptoms of the human ADHD pathology. In order to evaluate pathological forms of executive functions and impulsive behavior in 6-OHDA mice during young age, we first tested latent inhibition (LI) after weaning, and then we evaluated the impulsive behavior using a cliff avoidance reaction test. Our results demonstrated that 6-OHDA mice showed disruption in latent inhibition, suggesting a deficit in selective attention, and displayed repetitive peering-down behavior, indicating a maladaptive impulsive behavior. Subsequently, to assess impulsivity and attention in young mice, we performed a modified 5-choice serial reaction time task test (5-CSRTT), optimizing the degree of food restriction for young animals and shortening the training duration. This test allowed us to demonstrate a deficit in inhibitory control and a loss of accuracy of 6-OHDA mice in the 5-CSRTT. In conclusion, we demonstrated that the 6-OHDA mouse model reproduces human symptoms of ADHD in childhood and early adulthood periods, as seen in human. Taken together, the 6-OHDA mouse model will be useful alongside other animal models to understand the neurobiological mechanisms underlying complex, heterogeneous neurological disorders.
注意力缺陷多动障碍（ADHD）是一种以儿童注意力受损、冲动和多动为特征的综合征。这些症状在成人中也常常持续存在。在青春期，前额叶皮质与其他脑区建立连接，以发挥执行功能，如潜在抑制、注意力和抑制控制。在我们之前的工作中，我们证明了新生6-羟基多巴胺（6-OHDA）小鼠模型的有效性，这是一种模拟人类ADHD病理学主要症状的经典神经发育模型。为了评估幼年6-OHDA小鼠执行功能和冲动行为的病理形式，我们首先在断奶后测试潜在抑制（LI），然后使用悬崖回避反应测试评估冲动行为。我们的结果表明，6-OHDA小鼠的潜在抑制受到破坏，表明选择性注意力存在缺陷，并表现出重复的向下窥视行为，表明存在适应不良的冲动行为。随后为了评估幼年小鼠的冲动性和注意力，我们进行了改良的5选择连续反应时任务测试（5-CSRTT），优化了幼年动物的食物限制程度并缩短了训练时间。该测试使我们能够证明6-OHDA小鼠在5-CSRTT中存在抑制控制缺陷和准确性丧失。总之，我们证明了6-OHDA小鼠模型再现了人类儿童期和成年早期的ADHD症状。综上所述，6-OHDA小鼠模型将与其他动物模型一起有助于理解复杂的、异质性神经障碍背后的神经生物学机制。
