Conditioned compensatory responses elicited by environmental signals for cyclophosphamide-induced suppression of antibody production in mice

Abstract

Several investigators have reported that animals that receive taste cues paired with cyclophosphamide, an immunosuppressant drug, acquire a conditioned response that modifies the ability of the immune system to respond to antigenic stimulation (sheep red blood cells). Although most reports suggest that this conditioned response includes a suppression of antibody production, some investigators also have reported a conditioned enhancement of immune response. We investigated the conditioned response to environmental cues paired with cyclophosphamide. We discovered that, in contrast to the usual finding of conditioned suppression with taste cues, environmental cues elicit a compensatory conditioned response that reduces the residual suppression of antibody production caused by the drug. Additional evidence for compensatory conditioning was found in the relative weight gains of conditioned and unconditioned groups that were exposed to cyclophosphamide. Despite the clear development of a taste aversion in groups that were exposed to a taste cue in addition to the environmental cue, taste cues in compound with the environmental cues did not modify antibody production. These findings raise the possibility that previous reports of conditioned enhancement of immune response might be due to the presence of environmental cues.