Metabolic activity in the brain of juvenile and adult rats with a neonatal ventral hippocampal lesion.

Longitudinal studies on patients for schizophrenia suggest that functional brain perturbations precede the onset of symptoms. Rats with a neonatal ventral hippocampal lesion (NVHL) are considered as a heuristic neurodevelopmental model of schizophrenia. We characterized basal metabolic changes observed in NVHL rats before and after the age when known behavioral alterations have been reported. Male pups were lesioned with ibotenic acid at postnatal day 7 (PD7). We measured local cerebral metabolic rates for glucose (LCMRglc) by the quantitative autoradiographic [(14)C]2-deoxyglucose technique at pre- (PD21) and postpubertal (PD42) ages when NVHL rats do not express abnormal dopamine related behaviors, and at adulthood (PD70). We observed a widespread increase in LCMRglcs in PD21 NVHL indicative of an ongoing intense reorganization of the brain while at PD42, increases were less extended. At PD70, changes in glucose metabolism were restricted to specific systems, such as the auditory system, the cerebellum, the serotonergic median raphe, and median septum. These data show in a heuristic animal model of schizophrenia that functional metabolic changes within the brain could precede the onset of dopamine-related behavioral alterations and lead to a distinct ensemble of functional changes in adulthood in systems that may be relevant to schizophrenia. Copyright 2009 Wiley-Liss, Inc.