Acquisition and extinction of conditional immunoenhancement following training with cyclophosphamide

Paired-group mice were injected with pentobarbital (a pharmacological conditioned stimulus, CS) prior to injection of cyclophosphamide (Cy), an immunosuppressive drug. Unpaired-group mice received Cy 24 h after the CS. CS-alone mice received only pentobarbital. When reexposed to the CS in conjunction with an antigenic challenge, unpaired-group mice displayed suppressed antibody titers, while paired-group mice displayed titers similar to those of CS-alone mice. Thus, the residual immunosuppressive effect of Cy was eliminated by the Cy-paired cue. Subsequently half the mice in each group were repeatedly presented with the CS and half were left undisturbed. Mice were again challenged and reexposed to the CS. Unpaired-group mice now had titers equivalent to CS-alone mice, indicating that the immunosuppressive effect of Cy had dissipated. Results from paired-group mice indicated a frank conditional immunoenhancement that was extinguished by repeated CS presentations.