Prenatal methylazoxymethanol acetate alters behavior and brain NGF levels in young rats: a possible correlation with the development of schizophrenia-like deficits

It has been hypothesized that a deleterious key contribution to schizophren ia (SZ) development is a failure of migration and setting of young neurons into their appropriate cortical target sites, particularly in the entorhina l cortex (EC). To test this hypothesis in an animal model, we injected, in pregnant rats, on gestational day (GD) 9, or 10, or 11, or 12, the antimito tic compound methylazoxymethanolacetate (MAM) known to cause EC neuronal lo ss. We investigated whether or not EC disruption during prenatal developmen t is able to affect behavior, including memory and learning, and brain nerv e growth factor (NGF). Prenatally MAM treated young rats didn't display gro ss behavioral changes in social interaction, open-field and novel object in vestigation tests. By contrast, GD11 and GD12 MAM treated rats had a retard ation in passive avoidance acquisition, while, in GD12 animals, pain sensit ivity was reduced. GD12 animals also showed increased NGF in the EC and rem aining cortex. MAM treated animals showed no changes in paw NGF or substanc e P levels suggesting that the altered nociceptive response is not related to local downregulation of these two molecules. The possibility that these behavioral and biochemical alterations might be associated with the onset o f SZ is discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.