Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia

被引:269
作者
Breese, CR
Lee, MJ
Adams, CE
Sullivan, B
Logel, J
Gillen, KM
Marks, MJ
Collins, AC
Leonard, S
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA
[2] Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA
[3] Denver Vet Adm Med Ctr, Denver, CO USA
[4] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA
[5] Auburn Univ, Sch Pharm, Dept Pharmacal Sci, Auburn, AL 36849 USA
关键词
schizophrenia; cigarettes; human brain; nicotine; nicotinic receptors; postmortem; receptor binding; smoking;
D O I
10.1016/S0893-133X(00)00121-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous studies have suggested that an abnormality in neuronal nicotinic acetylcholine receptor expression or function may be involved in the neuropathophysiology of schizophrenia. [H-3]-nicotine and [H-3]-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. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
引用
收藏
页码:351 / 364
页数:14
相关论文
共 80 条
[1]   Schizophrenia, sensory gating, and nicotinic receptors [J].
Adler, LE ;
Olincy, A ;
Waldo, M ;
Harris, JG ;
Griffith, J ;
Stevens, K ;
Flach, K ;
Nagamoto, H ;
Bickford, P ;
Leonard, S ;
Freedman, R .
SCHIZOPHRENIA BULLETIN, 1998, 24 (02) :189-202
[2]   NORMALIZATION BY NICOTINE OF DEFICIENT AUDITORY SENSORY GATING IN THE RELATIVES OF SCHIZOPHRENICS [J].
ADLER, LE ;
HOFFER, LJ ;
GRIFFITH, J ;
WALDO, MC ;
FREEDMAN, R .
BIOLOGICAL PSYCHIATRY, 1992, 32 (07) :607-616
[3]  
ADLER LE, 1993, AM J PSYCHIAT, V150, P1856
[4]  
Albuquerque E. X., 1998, Society for Neuroscience Abstracts, V24, P1581
[5]  
Alkondon M, 1997, J PHARMACOL EXP THER, V283, P1396
[6]   CHARACTERIZATION OF N-[H-3]METHYLCARBAMYLCHOLINE BINDING-SITES AND EFFECT OF N-METHYLCARBAMYLCHOLINE ON ACETYLCHOLINE-RELEASE IN RAT-BRAIN [J].
ARAUJO, DM ;
LAPCHAK, PA ;
COLLIER, B ;
QUIRION, R .
JOURNAL OF NEUROCHEMISTRY, 1988, 51 (01) :292-299
[7]   Desensitization of the nicotinic acetylcholine receptor mainly involves a structural change in solvent-accessible regions of the polypeptide backbone [J].
Baenziger, JE ;
Chew, JP .
BIOCHEMISTRY, 1997, 36 (12) :3617-3624
[8]   EVIDENCE THAT TOBACCO SMOKING INCREASES THE DENSITY OF (-)-[H-3]NICOTINE BINDING-SITES IN HUMAN-BRAIN [J].
BENWELL, MEM ;
BALFOUR, DJK ;
ANDERSON, JM .
JOURNAL OF NEUROCHEMISTRY, 1988, 50 (04) :1243-1247
[9]   Nicotinic receptor mediates spontaneous gaba release in the rat dorsal motor nucleus of the vagus [J].
Bertolino, M ;
Kellar, KJ ;
Vicini, S ;
Gillis, RA .
NEUROSCIENCE, 1997, 79 (03) :671-681
[10]  
Blaha CD, 1996, J NEUROSCI, V16, P714