Paradoxical conditioning of the plasma copper and corticosterone responses to bacterial endotoxin

The cascade of physiologic mechanisms in response to infection, the acute phase response, is recognized as having a major role in host defense. Two such responses are an increase in plasma copper and activation of the hypothalamic-pituitary-adrenal axis, which are consistently reported to occur during bacterial infection. We aimed to determine whether the alterations in plasma copper and corticosterone were conditionable using the conditioned taste aversion paradigm. The regime involved the pairing of a novel-tasting saccharine solution (the conditioned stimulus) with lipopolysaccharide (the unconditioned stimulus). Seven days after the initial pairing of these stimuli (the test day), the saccharine solution was represented. Animals exposed to this condition displayed a significant decrease in plasma copper levels. In addition, these rats experienced a reduction in plasma corticosterone that was time dependent. Paradoxically, the conditioned response of both these variables were in a direction contrary to that reported during bacterial infection. These results suggest that some acute phase responses may condition as a rebound response, or in an opposing trend to that occurring as the initial reaction.