Drug-induced (poly I:C) pyrexic responses: Congruence with a compensatory conditioning analysis

Preliminary experiments indicated that DBA/2J mice exhibit a pyrexic response 4–6 h after injection with the synthetic, double-stranded polynucleotide, polyinosinic polycytidylic acid (poly I:C), a macrophage and natural killer (NK) cell activating compound. We tested the hypothesis that a procedure involving repeated paired delivery of odor cues and poly I:C would result in the elicitation of a conditioned “drug-compensatory” hypothermic response to a cued placebo injection. A 2 × 2 factorial design was employed in a two-phase experiment with mice. In the first phase, two groups of mice were given four weekly, signaled injections of either poly I:C (50 υg/mouse) or saline. Rectal temperature was taken immediately prior to the injection and at 1-h intervals for the next 6 h. During the second 4-week phase, half of the mice in the saline (S) and poly I:C (P) groups were maintained on the same drug regimen (S-S; P-P); the other half were shifted to the opposite drug condition (P-S; S-P). The results indicated that the mice given paired cue-drug delivery in Phase 1 demonstrated a robust hypothermic response to cued placebo injections in Phase 2 (Group P-S). This drug-compensatory hypothermic response was evident over all 4 weeks of testing. These results are consistent with the interpretation that drug-compensatory conditioning occurred to cues paired with poly I:C, and, more generally, our findings support the hypothesis that the effects of this immunostimulatory agent are subject to modificaton by the central nervous system.