Nicotinic receptors, smoking and schizophrenia

Neuronal nicotinic acetylcholine receptor expression was examined in schizo phrenia. The incidence of smoking in schizophrenia is remarkably high and n icotine has been found to normalize an auditory evoked potential deficit se en in most subjects who suffer from this disease. Antagonists and agonists of a specific subset of this receptor family, the alpha 7 nicotinic recepto r, were found to regulate the gating or filtering of auditory information i n both humans and in an animal model. The alpha 7 gene has been cloned and a polymorphic dinucleotide repeat near the gene was used for linkage analys is, showing the alpha 7 locus to be linked to the P50 deficit. Expression o f the alpha 7 receptor, which binds nicotine with low affinity, is reduced in the hippocampus of schizophrenics. [H-3]-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 su bjects. The results of these studies suggest the presence of abnormal expre ssion and function of the neuronal nicotinic receptor gene family in schizo phrenia.