Peele D B, Farmer J D, MacPhail R C
Toxicol Appl Pharmacol. 1987 May;88(3):397-410. doi: 10.1016/0041-008x(87)90214-6.
A series of studies investigated the conditioned flavor aversions induced by administration of either lead or thallium in combination with either dimercaprol or dimercaptosuccinic acid in an attempt to correlate changes in flavor-aversion conditioning to changes known to alter the toxicity of metal administration. Rats received po administration of either thallium sulfate or lead acetate given alone or in combination with either dimercaprol or dimercaptosuccinic acid after consuming saccharin. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving either lead or thallium showed significant reductions in saccharin preferences (i.e., conditioned flavor aversions). Rats receiving lead acetate in combination with either of the two chelators displayed significantly reduced conditioned flavor aversions when compared to the aversions induced in rats receiving lead alone. Under the same conditions, there were no differences in the conditioned flavor aversions of rats receiving thallium only and those of rats receiving thallium in combination with either of the two chelators. Attenuation of the lead-induced conditioned flavor aversions was eliminated when chelator administration was delayed by 4 hr. This attenuation of lead-induced but not thallium-induced aversions by dimercaprol and dimercaptosuccinic acid demonstrates the sensitivity and selectivity of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions and is in agreement with clinical reports of effective chelation therapy in cases of lead but not thallium intoxication.
一系列研究调查了单独给予铅或铊，以及给予二巯丙醇或二巯基丁二酸后诱导的条件性味觉厌恶，试图将味觉厌恶条件反射的变化与已知会改变金属给药毒性的变化联系起来。大鼠在摄入糖精后，经口给予硫酸铊或醋酸铅，单独给药或与二巯丙醇或二巯基丁二酸联合给药。三天后，让它们在饮用糖精和水之间进行选择，并记录对糖精的偏好。与未接受任何处理或仅接受赋形剂的大鼠相比，接受铅或铊的大鼠对糖精的偏好显著降低（即条件性味觉厌恶）。与仅接受铅的大鼠相比，接受醋酸铅与两种螯合剂之一联合给药的大鼠，其条件性味觉厌恶显著降低。在相同条件下，仅接受铊的大鼠和接受铊与两种螯合剂之一联合给药的大鼠的条件性味觉厌恶没有差异。当螯合剂给药延迟4小时时，铅诱导的条件性味觉厌恶的减弱消失。二巯丙醇和二巯基丁二酸对铅诱导而非铊诱导的厌恶的减弱作用，证明了味觉厌恶条件反射范式在表征金属 - 螯合剂相互作用方面的敏感性和选择性，并且与铅中毒而非铊中毒病例中有效螯合治疗的临床报告一致。
