Postweaning social isolation exacerbates neurotoxic effects of the NMDA receptor antagonist MK-801 in rats.

The glutamate hypothesis of schizophrenia postulates NMDA receptor hypofunction as important pathophysiological mechanism. In rodents, NMDA receptor antagonists induce together with psychosis-like effects cortical injury. Stress during adolescence can trigger schizophrenia by unknown mechanisms. Here we show in rats that juvenile chronic isolation significantly increases MK-801-triggered expression of heat shock protein 70, a marker of neuronal injury, in the retrosplenial cortex. These data suggest an additive effect of juvenile stress and NMDA receptor blockade, with possible relevance for schizophrenia.