Griffith J M, O'Neill J E, Petty F, Garver D, Young D, Freedman R
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA.
Biol Psychiatry. 1998 Jul 15;44(2):98-106. doi: 10.1016/s0006-3223(97)00362-4.
Nicotinic receptor dysfunction is a possible mechanism of the abnormal sensory gating observed in schizophrenia with the P50 auditory event-related potential. Although nicotinic receptors normally desensitize after activation by acetylcholine or nicotine, pathologically increased desensitization might cause receptor dysfunction in schizophrenia. To examine this possibility, central cholinergic neuronal activity was diminished by allowing schizophrenic patients to sleep briefly, after which they experienced a transient period of normal P50 gating, consistent with receptor resensitization during the absence of cholinergic stimulation. A critical test of the mechanism is whether this resensitization is blocked by concurrent administration of nicotine, which would provide continuous receptor stimulation.
Six schizophrenic patients repeated the sleep experiment during nicotine exposure from a dermal patch, in a double-blind, placebo-controlled design.
The normalization of P50 gating immediately postsleep was replicated in the placebo arm, but this effect was decreased in all six patients during exposure to nicotine.
The results suggest that nicotinic receptor desensitization is responsible for the loss of P50 gating in schizophrenia.
烟碱样受体功能障碍是精神分裂症中通过P50听觉事件相关电位观察到的异常感觉门控的一种可能机制。虽然烟碱样受体在被乙酰胆碱或尼古丁激活后通常会脱敏，但病理性增加的脱敏可能会导致精神分裂症中的受体功能障碍。为了检验这种可能性，通过让精神分裂症患者短暂睡眠来降低中枢胆碱能神经元活动，在此之后他们经历了一段短暂的正常P50门控期，这与在无胆碱能刺激期间受体再敏化一致。对该机制的一个关键测试是这种再敏化是否会被同时给予尼古丁所阻断，尼古丁会提供持续的受体刺激。
6名精神分裂症患者在使用皮肤贴片进行尼古丁暴露期间，以双盲、安慰剂对照设计重复睡眠实验。
安慰剂组在睡眠后立即出现的P50门控正常化得以重现，但在所有6名患者接触尼古丁期间，这种效应减弱。
结果表明，烟碱样受体脱敏是精神分裂症中P50门控丧失的原因。
