Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats

Behav Pharmacol. 2007 Mar;18(2):135-45. doi: 10.1097/FBP.0b013e3280d3ee83.


Isolation rearing has been used for inducing schizophrenia-like symptoms in rats. Human schizophrenics have deficits in prefrontal-dysfunction-related cognitive/behavioral flexibility. Rats with lesions of the medial prefrontal cortex perform poorly in reversal learning. It is uncertain whether isolation rearing, however, causes reversal-learning impairment in adult rats. Using the rotating T maze, this study examined the effect of chronic administration of clozapine on visual discrimination learning and reversal learning in isolation-reared and socially reared adult rats. The results show that isolation-reared rats without clozapine injection performed significantly worse than socially reared rats in reversal learning but not in acquisition learning. Chronic injection of clozapine (5 or 10 mg/kg) in isolation-reared rats significantly improved reversal learning but had no effects on acquisition learning. Further data analyses show that in both the inhibition phase and the new-strategy-acquisition phase of reversal learning, isolation-reared rats needed significantly more correct-response trials to reach the criterion than socially reared rats, and clozapine significantly reduced the isolation-induced impairment of reversal learning only in the new-strategy-acquisition phase. In socially reared rats, clozapine had a dose-related interfering effect on reversal learning but not acquisition learning. This study supports the use of isolation rearing as a model for investigating the neurodevelopmental hypothesis of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Clozapine / pharmacology*
  • Discrimination Learning / drug effects
  • Dose-Response Relationship, Drug
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / etiology
  • Learning Disabilities / psychology*
  • Male
  • Maze Learning / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reversal Learning / drug effects*
  • Social Isolation / psychology*
  • Visual Perception / drug effects


  • Antipsychotic Agents
  • Clozapine