Changes in gut bacteria have been shown to alter behavior in animal models of anxiety426, depression5, and social behavior7, but no previous studies have examined how changes in intestinal microbiota might affect behavioral responses to drugs of abuse. To assess how antibiotic depletion of the gut microbiota might affect the rewarding properties of cocaine, we performed an unbiased conditioned place preference (CPP) task for cocaine in mice treated with antibiotics and controls. Initial experiments were performed with a dose known to produce robust CPP (10 mg/kg). While this dose did produce the expected place preference in control animals, there was no difference between control and antibiotic-treated animals at this dose (Fig. 3a; two-tailed t-test: p = 0.84, t = 0.21). We next examined a low dose that does not lead to significant place preference in control animals (5 mg/kg). In these experiments we see that the antibiotic-treated mice demonstrate a robust place preference, while the control mice did not form a significant preference (Fig. 3b; p < 0.0001, t = 5.71). In control experiments in which both sides of the
