EFFECTS OF TYPICAL AND ATYPICAL ANTIPSYCHOTICS IN A PCP‐INDUCED BEHAVIORAL MODEL OF SCHIZOPHRENIA
Noelle Catherine Anastasio, Kenneth M Johnson
The FASEB Journal March 1, 2006 DOI: 10.1096/fasebj.20.4.a679-b (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rat pups |
| Interventions | Phencyclidine (PCP) Haloperidol Olanzapine Risperidone |
| Dose | PCP 10 mg/kg on postnatal days 7, 9, and 11; challenge dose 4 mg/kg PCP; haloperidol 0.1 mg/kg; olanzapine 1 mg/kg; risperidone 0.25 mg/kg |
| Duration | PCP treatment on postnatal days 7, 9, and 11; PPI measured on postnatal days 24-25; PCP challenge and locomotor activity measured on postnatal days 28-35 |
| Measures | pre-pulse inhibition (PPI) of acoustic startle, locomotor activity |
| Key findings | Neonatal PCP administration in rats produced a PPI deficit and locomotor sensitization. Haloperidol, olanzapine, and risperidone each prevented the PPI deficit, and risperidone also prevented locomotor sensitization. |
Abstract
Schizophrenia is a severe psychiatric disorder whose etiology is unknown; however, disruptions in glutamatergic and dopaminergic transmission may play a role. The NMDAR antagonist, phencyclidine (PCP), has been shown to mimic both the positive and negative symptoms of the disease and is widely used in animal studies as a model of schizophrenia. PCP administration results in increased locomotor activity and deficits in pre‐pulse inhibition (PPI) of acoustic startle. Locomotor sensitization is thought to model the positive symptoms while deficits in PPI are correlated to the negative symptoms of the disease. Sprague‐Dawley rat pups were treated with saline or PCP (10 mg/kg) on postnatal day (PN) 7, 9, and 11 and PPI was measured on PN24‐25. On PN28‐35 animals were administered a challenge dose of 4 mg/kg PCP and locomotor activity was measured. PCP administration resulted in a deficit in PPI as well as locomotor sensitization. Additional experiments tested the effect of pretreatment with the typical antipsychotic haloperidol or the atypical antipsychotics, olanzapine and risperidone. Haloperidol (0.1 mg/kg), olanzapine (1 mg/kg), and risperidone (0.25 mg/kg) were able to prevent the deficits in PPI caused by PCP administration. Risperidone (0.25 mg/kg) was also able to prevent locomotor sensitization in animals administered PCP. Future experiments will further investigate the role of haloperidol and olanzapine as well as selective DA and 5‐HT antagonists in this behavioral model of schizophrenia in order to determine the mechanism of protection by typical and atypical antipsychotics. Supported by DA‐07287, MH‐63871 and Eli Lilly and Co.