title: Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.
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.
authors.affiliation: Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. hirofuminosuke@gmail.com
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ouchi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ono
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000523:psychology*; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012934:Social Isolation; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D002110:Caffeine