NORMALIZATION BY NICOTINE OF DEFICIENT AUDITORY SENSORY GATING IN THE RELATIVES OF SCHIZOPHRENICS
NORMALIZATION BY NICOTINE OF DEFICIENT AUDITORY SENSORY GATING IN THE RELATIVES OF SCHIZOPHRENICS
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DOI：
10.1016/0006-3223(92)90073-9
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发表时间：
1992-10-01
影响因子：
10.6
通讯作者：
FREEDMAN, R
中科院分区：
文献类型：
--
作者：
ADLER, LE;HOFFER, LJ;FREEDMAN, R
P50听觉诱发对重复刺激反应的门控减少是精神分裂症的一种心理生理特征，这也存在于许多患者的亲属中。听觉感觉门控的动物模型表明，烟碱能神经传递是一个重要的神经元底物。这个实验的目的是确定感觉门控的缺陷是否可以通过给药尼古丁来逆转。有异常感觉门控的精神分裂症患者的不吸烟亲属被选为最初的双盲试验的对象，以避免精神药物的影响，这种影响可能使精神分裂症患者本身的试验复杂化。含尼古丁的口香糖在给药30分钟内使P50感觉门控增加到接近正常水平。这种效果是短暂的；P50门控在1小时内恢复到基线水平。服用安慰剂后没有观察到任何变化。在其中一名受试者中，抗胆碱酯酶抑制剂毒豆碱类似地使P50门控正常化。结果与尼古丁胆碱能神经传递可能介导精神分裂症家族性心理生理缺陷的假设一致。
Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia.