Neonatal Ventral Hippocampus Lesion Induces Increase in NO Levels Which is Attenuated by Subchronic Haloperidol Treatment

Haloperidol is a potent dopamine receptor antagonist and used to treat psychotic disorders, such as schizophrenia. Recent clinical and preclinical studies demonstrated the overactivity of the nitric oxide (NO) system in schizophrenia. Neonatal ventral hippocampal (nVH) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Here, we investigate first whether the nVH lesion causes changes in NO levels in different limbic brain regions in young adults, postnatal day (PD) 81, and second, whether haloperidol treatment from PD60 to PD81 reverses these changes, by determining the accumulation of nitrites. The results show that NO levels at the level of the prefrontal cortex, occipital cortex, and cerebellum are higher in the nVH lesion animals, and that the haloperidol, in part, attenuates these altered NO levels. The NO levels observed in the nVH lesion animals with and without haloperidol treatment may be relevant to behaviors observed in schizophrenia. Synapse 64:941-947, 2010. (C)2010 Wiley-Liss, Inc.