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Cyclophosphamide-induced aversions to saccharin-flavored tap water were observed in normal control rats, in rats subjected to varying numbers of cyclophosphamide injections prior to conditioning, and in rats similarly subjected to preconditioning saline injections. Both initial magnitude and resistance to extinction of a conditioned flavor aversion were found to be inverse functions of preconditioning familiarity with drug-induced illness. Six preconditioning cyclophosphamide injections markedly reduced both initial aversion magnitude and resistance to extinction. In contrast, three such injections failed to affect initial aversion magnitude and resulted in a small acceleration of extinction rate, while one preconditioning cyclophosphamide injection produced no observable effects. These findings depict preconditioning familiarity with illness as one important variable modulating the strength of conditioned flavor aversions and emphasize the importance of viewing resistance to extinction as one indicator of aversion strength.

Bait-shyness acquisition and resistance to extinction as functions of US exposure prior to conditioning