Effect of isolation rearing on the expression of AMPA glutamate receptors in the hippocampal formation

Abstract

Reduced glutamatergic signaling may contribute to cognitive dysfunction in schizophrenia. Glutamatergic synapses might be the site of primary abnormalities in this disorder with the dopaminergic changes being secondary to altered glutamatergic transmission. Isolation rearing of rats from weaning has been used as an experimental model for affective disorders like schizophrenia. In this immunohistochemistry study we evaluate the changes in the expression of GluR1 and GluR2 AMPA receptors in the hippocampus, amygdala and entorhinal cortex induced by isolation rearing. Two groups of Wistar rats (grouped and isolated, n = 6/each) were used. Isolation rearing induced a significant decrease in GluR1- and GluR2-immunopositive cells in the hippocampus. For GluR1 the reduction was 31% in the hilus of dentate gyrus (p = 0.02) and 47% in CA3 (p = 0.002). For GluR2 the reduction was 52% in the hilus of dentate gyrus (p < 0.0001) and 29% in CA1 (p = 0.002). Isolation rearing induced a non-significant decrease in GluR1-immunopositive cells in the basolateral amygdala (p = 0.066) while no alteration was found in the lateral nucleus (p = 0.657). For GluR2 no changes were induced by isolation in both nuclei of the amygdala. In the entorhinal cortex no apparent difference was seen in GluR1- or GluR2-immunopositive cells when isolated reared rats were compared to grouped rats. The results suggest that isolation rearing from weaning induces changes on the expression of AMPA glutamate receptors in the hippocampus similar to those reported for postmortem human brains with schizophrenia. These findings also contribute to additional evidence for using isolation rearing of rats from weaning as an animal model for schizophrenia.