THE EFFECTS OF SINGLE AND REPEATED PHENCYCLIDINE ADMINISTRATION ON [I-125] IOMAZENIL BINDING IN THE RAT-BRAIN

We measured [I-125] iomazenil binding, labeling the central-type benzo diazepine receptor in 37 discrete rat brain areas following single (7. 5 mg/kg, i.p.) and repeated (7.5 mg/kg/day x 14 days, i.p.) treatment with phencyclidine (PCP), a non-competitive antagonist of the N-methyl -D-aspartate(NMDA)-type glutamate receptor, using in vitro quantitativ e autoradiographic receptor binding assay. Both single and repeated PC P treatment produced heterogeneous changes in the rat brain in a simil ar manner, the magnitude of change in [I-125] iomazenil binding being generally greater in the repeated treatment group than in the single t reatment group. A significant increase in [I-125] iomazenil binding wa s observed in the superficial layer (layer I-IV) of the parietal corte x in both of the PCP treatment groups and the CA1 of the hippocampus o f the repeated PCP-treated group. There was a significant decrease in [I-125] iomazenil binding in the piriform cortex of the repeated PCP-t reated group. These results suggest that the blockade of NMDA receptor -mediated glutamatergic neurotransmission by PCP produces the compensa tional alterations in the central-type benzodiazepine receptor antagon ist binding, and that the observed diversity may be due to dissimilar modes of organizations between glutamatergic and the GABA (gamma-amino butyric acid)-benzodiazepine receptor complex. Copyright (C) 1996 Else vier Science Ltd.