Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine.
Janne Damm Andersen, Bruno Pouzet
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 1, 2004 DOI: 10.1038/sj.npp.1300394 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female Sprague-Dawley rats treated perinatally |
| Interventions | Phencyclidine (PCP) D-serine |
| Dose | 8.7 mg/kg s.c. |
| Duration | Treatment on postnatal days 7, 9, and 11; behavioral testing in adulthood |
| Measures | Morris water maze task |
| Key findings | Perinatal PCP treatment impaired spatial reversal and working memory in male rats, and D-serine reversed these deficits. |
Abstract
It has been suggested that perinatal treatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) induces transient neurodegeneration in the limbic and cortical structures of rats. Since dysfunction of these structures is associated with cognitive deficits in patients with schizophrenia, we studied the effects of subchronic treatment with PCP in perinatal rats with respect to spatial reference, reversal, and spatial working memories using the Morris water maze task in adulthood. In addition, we investigated the effect of D-serine, which has clinical relevance for the treatment of cognitive deficits in patients with schizophrenia. Our goal was to develop a neurodevelopmental model with predictive validity for the cognitive dysfunction described in patients with schizophrenia. Male and female Sprague-Dawley rats were treated with either saline or PCP (8.7 mg/kg s.c.) on days 7, 9, and 11, postnatal, and the long-term behavioral effects were investigated in adulthood. Male PCP-treated rats were slightly impaired during the spatial reference memory task, but strongly impaired during the reversal and spatial working memory tasks. Female rats were not significantly affected by this treatment. This cognitive deficit was reversed by chronic treatment with D-serine. We suggest that this model mimics some of the cognitive deficits of patients with schizophrenia and might be appropriate for the screening of putative antipsychotic agents for the treatment of these cognitive deficits.