Effect of pretreatment with risperidone on phencyclidine-induced disruptions in object recognition memory and prefrontal cortex parvalbumin immunoreactivity in the rat

Behav Brain Res. 2010 Mar 17;208(1):132-6. doi: 10.1016/j.bbr.2009.11.018. Epub 2009 Nov 13.


Sub-chronic administration of phencyclidine to the rat induces enduring cognitive and pathophysiological changes that resemble some features of schizophrenia. The present study aimed to determine if concurrent administration of the atypical antipsychotic, risperidone, could attenuate the effect of phencyclidine on object recognition memory and parvalbumin-containing neurons in the prefrontal cortex. Rats were administered phencyclidine at a dose of 2mg/kg i.p. bi-daily for 1 week, or vehicle. Half of the phencyclidine group was concurrently treated with risperidone (0.5mg/kg i.p.) twice daily for 10 days, beginning 3 days before the start of phencyclidine administration. Novel object recognition memory and subsequent brain analysis were assessed 6 weeks post-phencyclidine treatment. Phencyclidine produced a deficit in object recognition memory as measured by the discrimination ratio. In addition, 6 weeks post-phencyclidine, analysis of brains showed a reduction in expression of parvalbumin-immunoreactive neurons in the prefrontal cortex, with specific deficits observed in the prelimbic region, but not infralimbic or cingulate cortices. Concurrent administration of risperidone showed no protective effects against these deficits. These results show the importance of the sub-chronic phencyclidine rat in modelling cognitive and prefrontal pathophysiology observed in schizophrenia, but suggest that concurrent risperidone is not neuroprotective in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / pharmacology
  • Drug Administration Schedule
  • Functional Laterality
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / pathology*
  • Memory Disorders / prevention & control*
  • Neuropsychological Tests
  • Parvalbumins / metabolism*
  • Phencyclidine
  • Prefrontal Cortex / metabolism*
  • Rats
  • Recognition, Psychology / drug effects
  • Retention, Psychology / drug effects
  • Risperidone / administration & dosage*
  • Risperidone / pharmacology


  • Antipsychotic Agents
  • Parvalbumins
  • Phencyclidine
  • Risperidone