Affiliations: Department of Psychiatry, University of Colorado
Health Sciences Center, Denver, Colorado, USA | Department of Pharmacology, University of Colorado
Health Sciences Center, Denver, Colorado, USA | The Denver Veterans Affairs Medical Center, Denver,
Colorado, USA
Abstract: Neuronal nicotinic acetylcholine receptor expresssion was examined
in schizophrenia. The incidence of smoking in schizophrenia is remarkably high
and nicotine has been found to normalize an auditory evoked potential deficit
seen in most subjects who suffer from this disease. Antagonists and agonists of
a specific subset of this receptor family, the a7 nicotinic receptor, were
found to regulate the gating of filtering of auditory information in both
humans and in an animal model. The a7 gene has been cloned and a polymorphic
dinucleotide repeat near the gene was used for linkage analysis, showing the a7
locus to be linked to the P50 deficit. Expression of the a7 receptor, which
binds nicotine with low affinity, is reduced in the hippocampus of
schizophrenics. [3H]-nicotine binding, a measure of the high affinity nicotinic
receptors, was also decreased in schizophrenics and does not increase in
response to tobacco use, as is seen in control subjects. The results of these
studies suggest the presence of abnormal expression and function of the
neuronal nicotinic receptor gene family in schizophrenia.
