SCHIZOPHRENIA AND NICOTINIC RECEPTORS
SCHIZOPHRENIA AND NICOTINIC RECEPTORS
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DOI：
10.3109/10673229409017136
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发表时间：
1994-11-01
影响因子：
3.8
通讯作者：
WALDO, M
中科院分区：
文献类型：
--
作者：
FREEDMAN, R;ADLER, LE;WALDO, M
精神分裂症患者通常不能对环境的重要特征做出反应，并过滤掉不相关的刺激。这种功能障碍可能与潜在的抑制缺陷有关，即大脑改变对重复刺激敏感性的能力。负责这种抑制门控的神经元机制之一涉及海马体中胆碱能烟碱受体的激活。这些受体在许多从精神分裂症患者死后获得的海马脑组织标本中减少。在活的精神分裂症患者中，尼古丁刺激胆碱能受体可短暂地恢复对感觉刺激的抑制门控反应。许多精神分裂症患者都是重度吸烟者，但尼古丁受体的特性只倾向于短期激活，这可能解释了为什么吸烟只是一种短暂的症状治疗方法。本文综述了精神分裂症患者抑制性门控缺陷的临床现象，这种门控机制的神经生物学，以及一些精神分裂症患者可能在参与这种神经生物学功能的尼古丁胆碱能受体中存在遗传缺陷的证据。抑制性门控缺陷仅通过抗精神病药物部分正常化，因此是精神分裂症新治疗策略的目标。
Patients with schizophrenia often cannot respond to important features of their environment and filter out irrelevant stimuli. This dysfunction could be related to an underlying defect in inhibition - i.e., the brain's ability to alter its sensitivity to repeated stimuli. One of the neuronal mechanisms responsible for such inhibitory gating involves the activation of cholinergic nicotinic receptors in the hippocampus. These receptors are diminished in many specimens of hippocampal brain tissue obtained postmortem from schizophrenic patients. In living schizophrenic patients, stimulation of cholinergic receptors by nicotine transiently restores inhibitory gating of evoked responses to sensory stimuli. Many people with schizophrenia are heavy smokers, but the properties of the nicotinic receptor favor only short-term activation, which may explain why cigarette smoking is only a transient symptomatic remedy. This paper reviews the clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function. Inhibitory gating deficits are only partly normalized by neuroleptic drugs and are thus a target for new therapeutic strategies for schizophrenia.