UNCOUPLING OF GABA(A) AND BENZODIAZEPINE RECEPTOR-BINDING ACTIVITY INTHE HIPPOCAMPAL-FORMATION OF SCHIZOPHRENIC BRAIN

A recent postmortem study has reported that there is a widespread upre gulation of GABA(A) receptor binding activity throughout most subregio ns of the hippocampal formation of schizophrenic brain. The current st udy has been undertaken to determine whether the benzodiazepine (BZ) r eceptor, which is a component of the GABA(A) receptor complex, may als o be upregulated in schizophrenics. Using a low-resolution film autora diographic technique to localize [H-3]flunitrazepam binding, the subre gional and laminar distribution of specific BZ receptor binding was fo und to parallel that of the GABA(A) site, except in the area dentata w here BZ binding was approximately 73% higher in the outer molecular la yer. When BZ receptor binding was compared in the same normal control (n = 15) and schizophrenic (n = 8) cases in which the GABA(A) receptor was analyzed, there were very few differences noted between the two g roups, except for small, though significant, increases in the stratum oriens of CA3 (30%), the subiculum (20-30%) and the presubiculum (15-2 0%) of the patient group. These latter increases overlapped with the s ubregions and laminae in schizophrenics showing the most marked increa ses of GABA(A) receptor binding. Using a high-resolution technique to evaluate specific BZ receptor binding on different neuronal subtypes, no difference was observed on either pyramidal or nonpyramidal neurons of sector CA3 where GABA(A) receptor activity had been found to be si gnificantly increased on the latter neuronal subtype. The potential co nfounding effects of age, postmortem interval and exposure to either b enzodiazepine or neuroleptic drugs do not account for the lack of mark ed differences in BZ receptor binding in the schizophrenic group. Take n together, the results of this study are consistent with the possibil ity that defective GABAergic integration in schizophrenia may be assoc iated with an uncoupling in the regulation of the GABA(A) and BZ recep tors. (C) 1997 Elsevier Science B.V.