to those seen with CPP. At 10 mg/kg dosing there was a robust sensitization response across the five-day period for both groups using repeated-measures two-way ANOVA (Main effect of time: F(4,32) = 29.53; p < 0.0001). However, there was no effect of antibiotic treatment (F(1,8) = 0.1342; p = 0.72) or an antibiotic x time interaction (F(4,32) = 1.486; p = 0.23) (Fig. 3d). We then examined a 5 mg/kg dose which generally does not produce a sensitized drug response in this assay. In this experiment, there was a significant difference between the control and antibiotic-treated animals (Fig. 3e - F(1,7) = 19.44; p = 0.003). Only the antibiotic-treated mice showed an increased response over time, with a main effect of time for the experiment (F(4,28) = 3.231; p = 0.03). Taken together with the CPP data, these experiments demonstrate that reduction of intestinal microbiota results in increased sensitivity to the behavioral effects of cocaine.
