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Nicotinic receptor function in schizophrenia

S Leonard1, C Adams, C R Breese

  • 1Dept. of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.

Schizophrenia Bulletin
|January 1, 1996
PubMed
Summary
This summary is machine-generated.

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Schizophrenia

Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Schizophrenia is linked to sensory processing deficits, including the P50 auditory-evoked potential gating deficit.
  • The alpha 7 nicotinic receptor is implicated in an inhibitory pathway potentially underlying this deficit.

Purpose of the Study:

  • To investigate the role of the alpha 7 nicotinic receptor in the P50 gating deficit in schizophrenia.
  • To explore the genetic linkage of this deficit to the alpha 7 nicotinic receptor gene.

Main Methods:

  • Utilized animal models to test alpha 7 nicotinic receptor antagonists.
  • Analyzed postmortem hippocampal tissue from schizophrenia subjects for receptor expression.
  • Performed linkage analysis between the P50 deficit and DNA markers in schizophrenia pedigrees.

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Main Results:

  • Nicotine normalized the P50 deficit in non-gating subjects.
  • Alpha 7 nicotinic receptor antagonists blocked normal gating in an animal model.
  • Reduced alpha 7 receptor expression was observed in schizophrenia brains.
  • Positive linkage was found between the P50 deficit and DNA markers on chromosome 15, near the alpha 7 nicotinic receptor gene.

Conclusions:

  • The alpha 7 nicotinic receptor plays a role in sensory gating and is a potential endophenotype in schizophrenia.
  • Genetic linkage suggests the alpha 7 nicotinic receptor gene is a susceptibility locus for schizophrenia.
  • Further research into gene-environment interactions is crucial for understanding schizophrenia's pathobiology.