Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia.
Previous studies have suggested that an abnormality in neuronal nicotinic acetylcholine receptor expression or function may be involved in the neuropathophysiology of schizophrenia. [(3)H]-nicotine and [(3)H]-epibatidine binding were compared in postmortem brain from control and schizophrenic subjects with varying smoking histories. In control subjects, increased receptor binding was seen in hippocampus, cortex, and caudate with increasing tobacco use. In contrast, schizophrenic smokers had reduced nicotinic receptor levels in these brain regions compared to control smokers. Chronic haloperidol and nicotine treatment, in the rat, was used to assess neuroleptic effects on receptor up-regulation by nicotine. A significant increase in cortical nicotinic receptors was seen in both nicotine treated as well as haloperidol and nicotine co-treated animals, suggesting that the abnormal regulation of high affinity neuronal nicotinic receptors in schizophrenics following nicotine use was not related to chronic neuroleptic treatment.
Breese
C R
CR
Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Lee
M J
MJ
Adams
C E
CE
Sullivan
B
B
Logel
J
J
Gillen
K M
KM
Marks
M J
MJ
Collins
A C
AC
Leonard
S
S
D000157:Aconitine / Q000031:analogs & derivatives / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002648:Child; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012044:Regression Analysis; D012559:Schizophrenia / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*
D014150:Antipsychotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D009538:Nicotine; D006220:Haloperidol; C082748:epibatidine; D000157:Aconitine