A hyperglycinergic rat model for the pathogenesis of schizophrenia: preliminary findings

There is evidence of high glycine concentrations in the brains and peripher y of schizophrenics. In the forebrain, glycine plays a major role as a co-a gonist with glutamate at the excitatory N-methyl-D-aspartate (NMDA) recepto rs. This activity of glycine is involved in the normal functioning of the b rain in adulthood and during neurodevelopment, and it may also cause neurot oxicity and brain abnormalities when its concentrations are high. To test t he hypothesis that the high glycine concentrations observed in schizophreni cs play an etiologic role in schizophrenia, an animal model was tested wher e rats were made hyperglycinic from life in utero to adulthood. The hypergl ycinic rats showed abnormalities in sensory gating mechanisms, enlarged cer ebral ventricles and diminished hippocampal dimensions. All of these abnorm alities closely parallel observations reported in patients with schizophren ic psychoses. These results from a rat model suggest an etiologic role for high glycine concentration in the behavior and brain abnormalities of schiz ophrenic patients. (C) 1999 Elsevier Science B.V. All rights reserved.