Cited by 180Nicotinic Acetylcholine Receptors StudySchizophrenia research and treatmentSmoking Behavior and Cessation

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Smoking and schizophrenia: abnormal nicotinic receptor expression

Leonard, Sherry, Breese, Charles, Adams, Catherine, Benhammou, Khalid, Gault, Judith, Stevens, Karen, Lee, Michael, Adler, Lawrence, Olincy, Ann, Ross, Randal, Freedman, Robert·2000·European Journal of Pharmacology

DOI 10.1016/s0014-2999(00)00035-2

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Abstract

Biological and genetic evidence suggests a role for the neuronal nicotinic receptors in the neuropathophysiology of schizophrenia. Nicotine normalizes an auditory evoked potential deficit seen in subjects who suffer from the disease. Nicotinic receptors with both high and low affinity for nicotine are decreased in postmortem brain of schizophrenics compared to control subjects. The chromosomal locus of the human alpha-7 gene (15q14) is linked to the gating deficit with a lod of 5.3, and antagonists of the alpha-7 receptor (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in rodents. We have cloned the human alpha-7 gene and found it to be partially duplicated proximal to the full-length gene. The duplication is expressed in both the brain and in peripheral blood cells of normal subjects, but is missing in some schizophrenic subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia.

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Authors: Leonard, S., Breese, C., Adams, C., Benhammou, K., Gault, J., Stevens, K., Lee, M., Adler, L., Olincy, A., Ross, R., & Freedman, R.
Affiliations: Veterans Health Administration (US)
Auburn University (US)
Corresponding author: Leonard, Sherry
ORCID: Breese, Charles
Gault, Judith
Stevens, Karen
Ross, Randal
Freedman, Robert
Venue: European Journal of Pharmacology
Publisher: Elsevier BV
Published: 2000-03
Volume: 393
Issue: 1-3
Pages: 237-242
ISSN: 0014-2999 (ISSN-L)
DOI: 10.1016/s0014-2999(00)00035-2
OpenAlex: W2058494585
Cited by: 177
References: 70
Citations by year: 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 12
FWCI: 3.98
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Journal of Pharmacology (publishedVersion)
PubMed (publishedVersion)
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
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: schizophrenia, smoking, neuronal nicotinic acetylcholine receptors, gene expression, gene duplication, receptor gating, postmortem brain, alpha-bungarotoxin, methyllycaconitine, genetic linkage
MeSH terms: Animals, Brain, Chromosome Mapping, Chromosomes, Human, Pair 15, Cloning, Molecular, Disease Models, Animal, Humans, Leukocytes, Mononuclear, Nicotine, Receptors, Nicotinic, Schizophrenia, Smoking, Gene Expression, Mice, alpha7 Nicotinic Acetylcholine Receptor

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Smoking and schizophrenia: abnormal nicotinic receptor expression

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