Schizophrenia and nicotinic receptors

Robert Freedman, Lawrence E. Adler, Paula Bickford, William Byerley, Hilary Coon, C. Munro Cullum, Jay M. Griffith, Josette G. Harris, Sherry Leonard, Christine Miller, Marina Myles-Worsley, Herbert T. Nagamoto, Greg Rose, Merilyne Waldo

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition-i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

Original languageEnglish (US)
Pages (from-to)179-192
Number of pages14
JournalHarvard Review of Psychiatry
Volume2
Issue number4
DOIs
StatePublished - 1994

Fingerprint

Nicotinic Receptors
Schizophrenia
Cholinergic Receptors
Aptitude
Neurobiology
Brain
Nicotine
Antipsychotic Agents
Hippocampus
Smoking
Therapeutics

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Freedman, R., Adler, L. E., Bickford, P., Byerley, W., Coon, H., Cullum, C. M., ... Waldo, M. (1994). Schizophrenia and nicotinic receptors. Harvard Review of Psychiatry, 2(4), 179-192. https://doi.org/10.3109/10673229409017136

Schizophrenia and nicotinic receptors. / Freedman, Robert; Adler, Lawrence E.; Bickford, Paula; Byerley, William; Coon, Hilary; Cullum, C. Munro; Griffith, Jay M.; Harris, Josette G.; Leonard, Sherry; Miller, Christine; Myles-Worsley, Marina; Nagamoto, Herbert T.; Rose, Greg; Waldo, Merilyne.

In: Harvard Review of Psychiatry, Vol. 2, No. 4, 1994, p. 179-192.

Research output: Contribution to journalArticle

Freedman, R, Adler, LE, Bickford, P, Byerley, W, Coon, H, Cullum, CM, Griffith, JM, Harris, JG, Leonard, S, Miller, C, Myles-Worsley, M, Nagamoto, HT, Rose, G & Waldo, M 1994, 'Schizophrenia and nicotinic receptors', Harvard Review of Psychiatry, vol. 2, no. 4, pp. 179-192. https://doi.org/10.3109/10673229409017136
Freedman R, Adler LE, Bickford P, Byerley W, Coon H, Cullum CM et al. Schizophrenia and nicotinic receptors. Harvard Review of Psychiatry. 1994;2(4):179-192. https://doi.org/10.3109/10673229409017136
Freedman, Robert ; Adler, Lawrence E. ; Bickford, Paula ; Byerley, William ; Coon, Hilary ; Cullum, C. Munro ; Griffith, Jay M. ; Harris, Josette G. ; Leonard, Sherry ; Miller, Christine ; Myles-Worsley, Marina ; Nagamoto, Herbert T. ; Rose, Greg ; Waldo, Merilyne. / Schizophrenia and nicotinic receptors. In: Harvard Review of Psychiatry. 1994 ; Vol. 2, No. 4. pp. 179-192.
@article{9d9b16536f284ebd89ee53657963736d,
title = "Schizophrenia and nicotinic receptors",
abstract = "Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition-i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.",
author = "Robert Freedman and Adler, {Lawrence E.} and Paula Bickford and William Byerley and Hilary Coon and Cullum, {C. Munro} and Griffith, {Jay M.} and Harris, {Josette G.} and Sherry Leonard and Christine Miller and Marina Myles-Worsley and Nagamoto, {Herbert T.} and Greg Rose and Merilyne Waldo",
year = "1994",
doi = "10.3109/10673229409017136",
language = "English (US)",
volume = "2",
pages = "179--192",
journal = "Harvard Review of Psychiatry",
issn = "1067-3229",
publisher = "Informa Healthcare",
number = "4",

}

TY - JOUR

T1 - Schizophrenia and nicotinic receptors

AU - Freedman, Robert

AU - Adler, Lawrence E.

AU - Bickford, Paula

AU - Byerley, William

AU - Coon, Hilary

AU - Cullum, C. Munro

AU - Griffith, Jay M.

AU - Harris, Josette G.

AU - Leonard, Sherry

AU - Miller, Christine

AU - Myles-Worsley, Marina

AU - Nagamoto, Herbert T.

AU - Rose, Greg

AU - Waldo, Merilyne

PY - 1994

Y1 - 1994

N2 - Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition-i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

AB - Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition-i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=0028029650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028029650&partnerID=8YFLogxK

U2 - 10.3109/10673229409017136

DO - 10.3109/10673229409017136

M3 - Article

C2 - 9384901

AN - SCOPUS:0028029650

VL - 2

SP - 179

EP - 192

JO - Harvard Review of Psychiatry

JF - Harvard Review of Psychiatry

SN - 1067-3229

IS - 4

ER -