Backward conditioning of tumor necrosis factor-α in a single trial: Changing intervals between exposures to lipopolysaccharide and saccharin taste

The current study examined the effect of backward conditioning with three different time intervals between exposures to lipopolysaccharide (LPS) as the unconditioned stimulus (US) and saccharin taste in water as the potential conditioned stimulus (CS). Forty-eight naïve female BALB/c mice at three months of age served as subjects, divided into six groups. Four groups were assigned to Experiment 1 for the tumor necrosis factor alpha (TNF-α) measure, and the remaining two groups were used in Experiment 2 to measure taste aversion behavior. Both experiments employed a single trial. The timing of introduction to the saccharin taste varied between 3 min, 7 h, and 24 h following an LPS injection in Experiment 1. Experiment 2 employed the three-minute interval only. These intervals correspond to distinct immunological, physiological, and behavioral events induced by LPS. On the day after re-exposure to the saccharin taste, the TNF-α groups were challenged with LPS to test the LPS tolerance response. While backward conditioning of taste aversion behavior was not observed, some evidence of conditioned TNF-α response and subsequent development of LPS tolerance was observed with backward conditioning in a single trial. This exploratory study demonstrated that the effect of backward conditioning on conditioned TNF-α response and LPS tolerance response in a single trial depended on the timing of when a CS is presented after LPS exposure.

Research Highlights► We examined the effect of backward conditioning with LPS on TNF-alpha. ► We used the saccharin taste presenting with three different intervals. ► Taste aversion behavior did not develop. ► The evidence of various conditioned TNF-alpha response and LPS tolerance was observed.