EVIDENCE IN POSTMORTEM BRAIN-TISSUE FOR DECREASED NUMBERS OF HIPPOCAMPAL NICOTINIC RECEPTORS IN SCHIZOPHRENIA

This study rests the hypothesis that nicotinic cholinergic receptors, including those sensitive to the antagonist alpha-bungarotoxin, are de creased in the hippocampus of schizophrenics. The hypothesis is derive d from the finding that alpha-bungarotoxin causes a defect in the inhi bitory, gating of auditory-evoked potentials in laboratory animals tha t resembles a defect in auditory sensory gating observed in schizophre nics. Nicotine transiently normalizes this psychophysiological deficit in schizophrenic patients. Postmortem brain tissue was obtained from eight schizophrenic and eight age-matched nonschizophrenic subjects, S ections of the hippocampus were labeled with [(125) I]-alpha-bungaroto xin and imagined by autoradiography. Binding of the nicotinic agonist [H-3]-cytisine was determined in tissue hormogenates, alpha-Bugarotoxi n labeled a population of putative interneurons in the hippocampus, pr imarily in the dentate gyrus and the CA3 region of Ammon's hem. This l abeling was significantly decreased in the tissue from the schizophren ic patients, with seven or eight patients below the range of the nonsc hizophrenic subjects, There was also a significant decrease in the bin ding of cytisine, The results were not related to generalized hippocam pal cell loss, drug exposure at time of death, or smoking history, Thi s initial study suggests that schizophrenic patients have fewer nicoti nic receptors in the hippocnmpus, a condition which may lead to failur e of cholinergic activation of inhibitory interneurons, manifest clini cally as decreased gating of response to sensory stimulation.