Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder

Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

doi:10.1016/j.bbr.2012.10.029

Cited by 64Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder

Ouchi, Hirofumi, Ono, Kazuya, Murakami, Yukihisa, Matsumoto, Kinzo·2013·Behavioural Brain Research

DOI 10.1016/j.bbr.2012.10.029

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Abstract

Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit.

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“The time spent exploring the novel object and the familiar object was measured based on Ennaceur and Delacour (1988) and adapted from the task by Ouchi et al (2013).”
Method
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“7 difficulties amongst individuals with neurodevelopmental conditions, prevent the development of greater social competence (Koegel, 2000) and may also promote hyperactivity (Ouchi et al., 2013; Sullens et al., 2021).”
Background
Posterior parietal cortex contributions to cross-modal brain plasticity upon sensory loss
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Kami-shoyo-san improves ASD-like behaviors caused by decreasing allopregnanolone biosynthesis in an SKF mouse model of autism
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Addressing the Complexity of Tourette's Syndrome through the Use of Animal Models
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Sansoninto, a traditional herbal medicine, ameliorates behavioral abnormalities and down-regulation of early growth response-1 expression in mice exposed to social isolation stress
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Methionine Administration in Pregnant Rats Causes Memory Deficit in the Offspring and Alters Ultrastructure in Brain Tissue
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“This task was based on Ennaceur and Delacour (1988) and adapted from the task by Ouchi et al. (2013) with some modifications.”
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Promises of Caffeine in Attention-Deficit/Hyperactivity Disorder: From Animal Models to Clinical Practice
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Exhaustive Multi-Parametric Assessment of the Behavioral Array of Daily Activities of Mice Using Cluster and Factor Analysis
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“Post-weaning (at 4 weeks old) social isolation was reported to cause the most severe and long-lasting changes, such as aggression, cognitive rigidity, hyper-locomotor activity, impaired fear memory, reduced prefrontal cortical volume, decreased cortical and hippocampal synaptic plasticity (Fone and Porkess, 2008; Ouch…”
Background
Altered dorsal functional connectivity after post-weaning social isolation and resocialization in mice
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Areas of Convergence and Divergence in Adolescent Social Isolation and Binge Drinking: A Review
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Adenosinergic system and nucleoside transporters in attention deficit hyperactivity disorder: Current findings
Valladão, S. C., França, A. P., Pandolfo, P., & dos Santos‐Rodrigues, A. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105771 · Cited by 8 · see citing works
Celastrus paniculatus oil ameliorates synaptic plasticity in a rat model of attention deficit hyperactivity disorder
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Haloperidol rescues the schizophrenia-like phenotype in adulthood after rotenone administration in neonatal rats
Varga, T. G., Simões, J. G. D. T., Siena, A., Henrique, E., da Silva, R. C. B., Bioni, V. S., Ramos, A. C., & Rosenstock, T. R. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05880-1 · Cited by 9 · see citing works
Contribution of animal models to contemporary understanding of Attention Deficit Hyperactivity Disorder
Carvalho, C. (2016) · ALTEX · doi:10.14573/altex.1507311 · Cited by 8 · see citing works
“Within ADHD, animals are used to model ADHD-related behaviors and traits (Yen et al., 2013), to seek understanding of ADHD’s biochemical pathways (Yen et al., 2013; Huang et al., 2015) as well as responses to putative drugs (Dudley et al., 2013) and other therapies (Ouchi et al., 2013).”
Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?
Mysliveček, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.716460 · Cited by 6 · see citing works
“Other effects of social isolation include changes in learning (Petkov and Rousseva, 1984; Wongwitdecha and Marsden, 1996; Ouchi et al., 2013), anxiety (Cheeta et al.”
BackgroundInfluential
Early life adversity and adult attention-deficit/hyperactivity disorder (ADHD): Pathways to persistence and adult susceptibility
Zou, P., Huang, Z., Zong, X., & Zhang, Q. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106436 · Cited by 5 · see citing works
Consumption of a palatable diet rich in simple sugars during development impairs memory of different degrees of emotionality and changes hippocampal plasticity according to the age of the rats
Torre, V. A., Machado, A. G., Pereira, N. D. S. C., Arcego, D. M., Vieira, A. D. S., Salerno, P. S. V., Garcia, E. D. S., Lazzaretti, C., Toniazzo, A. P., Nedel, F., et al. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10032 · Cited by 5 · see citing works
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Pavlova, I. V., & Broshevitskaya, N. D. (2021) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093021040062 · Cited by 4 · see citing works
“After SI the fear conditioning was disrupted; when tested 24 h after training, the animals froze less only after applying context [25, 35, 36], con text and cue [21, 24, 27, 28], or only cue [26].”
BackgroundMethod
Effect of Sopoongsan on Skin Inflammation and Hyperlocomotion in Socially Isolated Mice with Atopic Dermatitis
Nguyen, L. T. H., Choi, M.-J., Shin, H., & Yang, I. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/3323201 · Cited by 4 · see citing works
“Previous studies have suggested that SI stress could induce ADHD symptoms, including hyper-locomotion, spatial attention deficit, and aggressive behavior in rodents [64,65].”
Background
Sansoninto attenuates aggressive behavior and increases levels of homovanillic acid, a dopamine metabolite, in social isolation-reared mice
Watanabe, T., Iba, H., Moriyama, H., Kubota, K., Katsurabayashi, S., & Iwasaki, K. (2021) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2021.08.006 · Cited by 3 · see citing works
The Use of Object Recognition Task in Animal Models of Attention-Deficit Hyperactivity Disorder
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Circadian Clocks, Stress, and Psychiatric Disorders
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Effect of caffeine on hippocampal memory and levels of gene expression in social isolation stress
Keloğlan, S., Şahin, L., Kocahan, S., Annaç, E. E., Tiraşçi, N., & Pekmezekmek, A. B. (2023) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10292 · Cited by 2 · see citing works
“Ouchi et al. found that exposure to SI from PND28 causes spatial attention deficit in mice, and Cf (0.5 – 1 mg/kg, i.p.) improved the SI-induced latent learning deficit (Ouchi et al., 2013).”
BackgroundInfluential
Cognitive Consequences of Social Isolation During COVID-19: side effects and treatmentsPreprint
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SOSYAL İZOLASYONUN NEDEN OLDUĞU STRESİN OKSİDATİF STRES BELİRTEÇLERİ VE ÖĞRENME İLE İLİŞKİLİ NÖROGRANİN/ CAMKII/CREB PROTEİNLERİNE ETKİSİ
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Social Isolation Induces Nest-Building Deficits in Juvenile MicePreprint
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Authors: Ouchi, H., Ono, K., Murakami, Y., & Matsumoto, K.
Affiliations: University of Toyama (JP)
Corresponding author: Matsumoto, Kinzo
ORCID: Matsumoto, Kinzo
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2013-02
Volume: 238
Pages: 146-153
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2012.10.029
OpenAlex: W2116325315
Cited by: 64
References: 47
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 3
FWCI: 3.42
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology (24659347)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: social isolation, attention deficit hyperactivity disorder, latent learning, spatial attention, fear memory, methylphenidate, caffeine, cholinergic system, resocialization, mice
MeSH terms: Aggression, Central Nervous System Stimulants, Animals, Attention, Attention Deficit Disorder with Hyperactivity, Caffeine, Disease Models, Animal, Fear, Female, Learning, Male, Methylphenidate, Mice, Inbred ICR, Motor Activity, Social Isolation, Spatial Behavior, Recognition, Psychology, Mice

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Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder

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