Conditional immunomodulation following training with cyclophosphamide

In 5 experiments, paired-group rats received a conditional stimulus (CS) paired with the immunosuppressive drug cyclophosphamide (CY). In Experiments 1-3, the CS was saccharin (SAC). Consistent with previous reports, these rats acquired a SAC aversion. However, there was no evidence of conditional immunosuppression. Rather, when reexposed to SAC in conjunction with an antigenic challenge, paired-group rats evidenced hemagglutination antibody titers similar to those seen in rats that never received the immunosuppressant. That is, the usual effect of CY in compromising immunological functioning was attenuated or eliminated by the CY-paired flavor. The findings of Experiments 1-3 were confirmed in Experiments 4-5, which used nongustatory CSs. Both audiovisual (noise and flashing-light) and pharmacological (pentobarbital) cues were also effective signals for CY injection. Following pairing with CY, these cues protected animals from the immunosuppressive effects of the drug.