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Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia
Abstract
This study tests the hypothesis that nicotinic cholinergic receptors, including those sensitive to the antagonist alpha-bungarotoxin, are decreased in the hippocampus of schizophrenics. The hypothesis is derived from the finding that alpha-bungarotoxin causes a defect in the inhibitory gating of auditory-evoked potentials in laboratory animals that resembles a defect in auditory sensory gating observed in schizophrenics. Nicotine transiently normalizes this psychophysiological deficit in schizophrenic patients. Postmortem brain tissue was obtained from eight schizophrenic and eight age-matched nonschizophrenic subjects. Sections of the hippocampus were labeled with [125I alpha-bungarotoxin and imagined by autoradiography. Binding of the nicotinic agonist [3H]-cytisine was determined in tissue homogenates. alpha-Bungarotoxin labeled a population of putative interneurons in the hippocampus, primarily in the dentate gyrus and the CA3 region of Ammon's horn. This labeling was significantly decreased in the tissue from the schizophrenic patients, with seven or eight patients below the range of the nonschizophrenic subjects. There was also a significant decrease in the binding of cytisine. The results were not related to generalized hippocampal cell loss, drug exposure at time of death, or smoking history. This initial study suggests that schizophrenic patients have fewer nicotinic receptors in the hippocampus, a condition which may lead to failure of cholinergic activation of inhibitory interneurons, manifest clinically as decreased gating of response to sensory stimulation.
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“Thus, there is convergence between the genetic findings and the neurobiological model, corroborated by postmortem findings of decreased α7-nicotinic receptors in schizophrenia (31).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [31]
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Metadata
- Authors
- Freedman, R., Hall, M., Adler, L. E., & Leonard, S.
- Affiliations
- Denver VA Medical Center (US)
- University of Colorado Denver (US)
- Corresponding author
- Freedman, Robert
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1995-07
- Volume
- 38
- Issue
- 1
- Pages
- 22-33
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2090019512
- Cited by
- 678
- References
- 55
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 12 · 2022: 11 · 2021: 16 · 2020: 18 · 2019: 17 · 2018: 11 · 2017: 17 · 2016: 18 · 2015: 34 · 2014: 29 · 2013: 27 · 2012: 30
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k01mh000728-01a1)
- National Institute of Mental Health (MH-44212, MH00728, MH 38321, P50MH044212)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, nicotinic acetylcholine receptors, hippocampus, alpha-bungarotoxin binding, auditory gating, inhibitory interneurons, dentate gyrus, CA3 region, postmortem brain, cholinergic dysfunction
- MeSH terms
- Quinolizidine Alkaloids, Adult, Aged, Alkaloids, Autoradiography, Azocines, Binding Sites, Bungarotoxins, Cell Count, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Quinolizines, Receptors, Nicotinic, Schizophrenia, Cholinergic Agents, Dentate Gyrus, Culture Techniques
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