On the effect of neonatal nitric oxide synthase inhibition in rats: a potential neurodevelopmental model of schizophrenia

NADPH-d (nicotinamide-adenine dinucleotide phosphate-diaphorase) neurons ar e thought to migrate improperly during development in the brains of schizop hrenic patients. This enzyme is a nitric oxide synthase (NOS). Nitric oxide (NO) is known to affect neurodevelopmental processes in the CNS. Therefore , we hypothesized that interference of NO generation during development may produce some aspects of schizophrenia symptomatology in a rat model. In th ese experiments, neonatal rats were challenged with a NOS inhibitor (L-nitr oarginine 1-100 mg/kg s.c.) daily on post-natal days 3-5. L-Nitroarginine ( L-NoArg) treated male rats developed a hypersensitivity to amphetamine in a dulthood versus vehicle treated controls, whereas female rats did not. Howe ver, L-NoArg treated female rats developed a hypersensitivity to phencyclid ine (PCP) at juvenile and adult ages versus vehicle treated controls, where as male animals did not. L-NoArg treated male rats also had deficits in pre -pulse inhibition of startle whereas adult female rats did not. The results are discussed in terms of a new neurodevelopmental model of schizophrenia and male/female differences inherent in this disease. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.