METHYLAZOXYMETHANOL ACETATE-INDUCED ABNORMALITIES IN THE ENTORHINAL CORTEX OF THE RAT - PARALLELS WITH MORPHOLOGICAL FINDINGS IN SCHIZOPHRENIA

It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neuro development. Furthermore, post-mortem studies show neuropathology of a pparently developmental origin in the entorhinal cortex and other brai n regions of schizophrenic subjects. In an attempt to model a developm ental defect of the entorhinal region in the rat, cerebrocortical prol iferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifical ly, the experimental set-up involved the administration of methylazoxy methanol acetate (MAM) on 1 of 4 consecutive days of embryonal develop ment, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these d ays. This effect shifts from lateral to medial divisions of the entorh inal cortex with later administration of MAM, following a known develo pmental gradient. Morphological consequences of MAM administration app ear to be largely confined to the entorhinal cortex in the groups trea ted on E9 to E11, although slight reductions of the frontal and occipi tal neocortex were also observed in these animals. MAM treatment on E1 2 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormaliti es are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorga nised cortical layering, and abnormal temporal asymmetries. These find ing bare some similarity to observations in brains of schizophrenic su bjects. The possible relevance of this approach in modeling neurodevel opmental aspects of schizophrenia is discussed. (C) 1998 Elsevier Scie nce B.V.