Behavioral and neurochemical alterations following repeated phencyclidine administration in rats with neonatal ventral hippocampal lesions

Exposure to chronic phencyclidine (PCP) has been reported to mimic certain aspects of schizophrenia in normal subjects as well as to exacerbate sympto ms in schizophrenic patients. Analogous to schizophrenics, adult rats with neonatal ventral hippocampal (VH) lesions have been shown to display enhanc ed sensitivity to both stress and psychostimulants. In order to examine whe ther repeated PCP treatment can modulate behavior when administered to neon atal VH-lesioned animals, we examined locomotor activity and immobility tim e in the forced swimming test (FST) in neonatal VH-lesioned rats following repeated PCP treatment. Receptor autoradiography studies were also performe d for dopamine (DA) and N-methyl-D-aspartate (NMDA) receptors to identify n eurochemical correlates of the altered behavior in these animals. Though re peated PCP administration resulted in increased levels of locomotor activit y and rearing in both VH-lesioned as well as sham rats, the effects were mu ch more enhanced in the lesioned rats compared to sham. However, repeated P CP treatment induced hypolocomotion during the habituation period in both s ham and lesioned rats. In the FST paradigm, lesioned rats displayed an alte red retention of acquired immobility. Repeated PCP administration increased DA D1-like receptors in the caudate-putamen in lesioned rats and decreased striatal D2-like receptors in both sham and lesioned rats. Moreover, repea ted PCP administration in lesioned rats decreased NMDA binding sites in the prefrontal cortex while increasing labelling in the subcortical regions. T hese results suggest that repeated administration of PCP can qualitatively and quantitatively affect behaviors in neonatal VH-lesioned rats related to abnormal neurodevelopmental processes presumably via prefrontal glutamater gic and subcortical dopaminergic dysfunctions. (C) 2000 Elsevier Science Lt d. All rights reserved.