Overstreet D H, Miller C S, Janowsky D S, Russell R W
Center for Alcohol Studies, University of North Carolina, Chapel Hill 27599-7178, USA.
Toxicology. 1996 Jul 17;111(1-3):119-34. doi: 10.1016/0300-483x(96)03370-7.
Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.
多重化学物质敏感症（MCS）是一种临床现象，即个体在急性或间歇性接触一种或多种化学物质（通常是有机磷酸酯类农药（OPs））后，会对多种化学性质无关的化合物变得过度敏感，这些化合物可能包括乙醇、咖啡因和其他精神药物。与对照品系弗林德斯抗性品系（FRL）大鼠相比，弗林德斯敏感品系（FSL）大鼠经过选择性培育，对有机磷酸酯类二异丙基氟磷酸酯（DFP）更为敏感。本文将总结相关证据，这些证据表明FSL大鼠与患有MCS的个体表现出某些相似之处。除了对DFP更敏感外，FSL大鼠对尼古丁以及毒蕈碱激动剂槟榔碱和氧化震颤素也更敏感，这表明胆碱能受体的数量可能增加，这一结论现在得到了生化证据的支持。还发现FSL大鼠对多种其他药物表现出增强的反应，包括5-羟色胺激动剂间氯苯基哌嗪和8-羟基二丙胺基四氢萘、多巴胺拮抗剂雷氯必利、苯二氮䓬类地西泮和乙醇。MCS患者报告称对这些药物中的许多药物反应增强，这表明FSL大鼠和MCS患者之间存在一些相似之处。与FRL对照相比，FSL大鼠还表现出活动和食欲减少以及快速眼动睡眠增加。由于在人类抑郁症患者中也观察到这些行为特征和增强的胆碱能反应，因此FSL大鼠已被提议作为抑郁症的遗传动物模型。也有报道称，MCS患者在化学敏感性发作之前和之后患抑郁症的发生率都更高，因此胆碱能超敏反应可能是一种使个体易患抑郁症和/或MCS的状态。进一步探索MCS患者、人类抑郁症患者和FSL大鼠之间的共性和差异，将有助于阐明MCS的潜在机制，并可能导致有利于MCS患者的诊断方法和治疗方法。
