Conditioned flavor aversions: Applications in assessing the efficacy of chelators in the treatment of heavy-metal intoxication

Abstract

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.