Neonatal 6-OHDA Lesion Model in Mouse Induces Cognitive Dysfunctions of Attention-Deficit/Hyperactivity Disorder (ADHD) During Young Age
Front. Behav. Neurosci.. 2020-02-26; 14:
DOI: 10.3389/fnbeh.2020.00027
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1. Front Behav Neurosci. 2020 Feb 26;14:27. doi: 10.3389/fnbeh.2020.00027.
eCollection 2020.
Neonatal 6-OHDA Lesion Model in Mouse Induces Cognitive Dysfunctions of
Attention-Deficit/Hyperactivity Disorder (ADHD) During Young Age.
Bouchatta O(1)(2)(3), Manouze H(1), Ba-M’Hamed S(1), Landry M(2)(3), Bennis M(1).
Author information:
(1)Laboratory of Pharmacology, Neurobiology and Behavior, Faculty of Sciences,
Cadi Ayyad University, Marrakesh, Morocco.
(2)University of Bordeaux, Bordeaux, France.
(3)CNRS UMR 5297, Centre Paul Broca-Nouvelle Aquitaine, Interdisciplinary
Institute of Neuroscience, Bordeaux, France.
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.
Copyright © 2020 Bouchatta, Manouze, Ba-M’Hamed, Landry and Bennis.
DOI: 10.3389/fnbeh.2020.00027
PMCID: PMC7054716
PMID: 32174817