Behavioral abnormality and pharmacologic response in social isolation-reared mice

Behav Brain Res. 2009 Aug 24;202(1):114-21. doi: 10.1016/j.bbr.2009.03.028. Epub 2009 Mar 31.


Social isolation (SI) rearing in rodents causes a variety of behavioral changes, including hyperlocomotion, anxiety, impulsivity, aggression, and learning and memory deficits. These behavioral abnormalities in rodents may be related to the symptoms in patients with neuropsychiatric disorders, such as attention-deficit hyperactivity disorder, obsessive-compulsive disorder, autism, schizophrenia and depression. In this study, we examined the effect of long-term SI rearing after weaning on emotional behaviors and cognitive function in mice. Furthermore, the effects of methylphenidate (MPH), clozapine (CLZ) and fluoxetine (FLX) on SI-induced behavioral changes were examined to measure the predictive validity of SI-reared mice as an animal model for these neuropsychiatric disorders. MPH improved SI-induced anxiety-like behavior in the elevated-plus maze test, but had no effect on aggressive behavior. In contrast, CLZ ameliorated aggressive behavior, but not anxiety-like behavior in SI-reared mice. Repeated FLX treatment prevented SI-induced aggressive behavior and social interaction deficits. These findings suggest that SI-induced behavioral abnormality is a psychobehavioral complex relevant to various clinical symptoms observed in neuropsychiatric disorders and that SI-reared mice are a useful animal model to study the pathophysiology/pathogenesis of these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects
  • Aggression / psychology
  • Animals
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antipsychotic Agents / administration & dosage
  • Anxiety / drug therapy
  • Anxiety / psychology
  • Behavior, Animal / drug effects*
  • Central Nervous System Stimulants / administration & dosage
  • Clozapine / administration & dosage
  • Cognition / drug effects*
  • Emotions / drug effects*
  • Fluoxetine / administration & dosage
  • Male
  • Methylphenidate / administration & dosage
  • Mice
  • Mice, Inbred ICR
  • Social Behavior
  • Social Isolation / psychology*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / psychology


  • Antidepressive Agents, Second-Generation
  • Antipsychotic Agents
  • Central Nervous System Stimulants
  • Fluoxetine
  • Methylphenidate
  • Clozapine