Interruptions of early cortical development affect limbic association areas and social behaviour in rats; possible relevance for neurodevelopmental disorders

Deficits in social behaviour are found in several neuropsychiatric disorder s with a presumed developmental origin. Adequate social behaviour may rely importantly on the associative integration of new stimuli with previously s tored, related information. The limbic allocortex, in particular the entorh inal region, is thought to support this kind of processing. Therefore, in t he present study, gestating dams were treated with methylazoxymethanol acet ate (MAM) on one of gestational days nine to twelve, to interrupt neuronal proliferation in the entorhinal region of the developing foetuses. Effects of prenatal MAM administration on social behaviour were evaluated in adult animals. As the entorhinal cortex has been implicated by some studies in sp atial memory, effects on this function were also investigated. Following th e behavioural studies, brain morphology was screened for effects of MAM. Ou r results show moderate to severe social impairment in MAM-treated animals, depending on the exact timing of prenatal exposure. By contrast, spatial r eference and working memory were not importantly affected in any group. Ana lysis of brain morphology in the MAM-treated offspring supported maldevelop ment of the entorhinal cortex and revealed mild abnormalities also in some connected limbic and Limbic affiliated structures, such as the perirhinal a nd ectorhinal cortex, the anterior cingulate cortex and the medial septum-d iagonal band region. Findings are discussed with respect to entorhinal cort ex function, and with regard to their relevance for psychiatric disorders w ith a putatively neurodevelopmental pathogenesis, such as schizophrenia. (C ) 1999 Elsevier Science B.V. All rights reserved.