THE GLYCINE NMDA RECEPTOR ANTAGONIST, L-701,324 REVERSES ISOLATION-INDUCED DEFICITS IN PREPULSE INHIBITION IN THE RAT

Previous studies have demonstrated that the glycine/NMDA receptor anta gonist, L-701,324 chloro-4-hydroxy-3(3-phenoxy)phenyl-2(H)quinolone) b locks the activation of mesolimbic dopamine systems induced following psychostimulant administration in the rat (Bristow et al. 1994). In th e present study, pretreatment with L-701,324 also reversed the deficit in prepulse inhibition (PPI) observed in rats reared in social isolat ion after weaning. Given that PPI is also attenuated in schizophrenic patients and that isolation rearing induces both neurochemical and beh avioural abnormalities suggestive of a physiologically induced state o f dopaminergic hyperactivity, these results suggest that blockade of t he glycine/NMDA receptor may offer a new strategy for the development of novel antipsychotic agents.