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. 2018 Mar 22;2:193–209. doi: 10.1016/j.isci.2018.03.003

Figure 1.

Figure 1

Antinociceptive Morphine Tolerance in Mice Is Prevented by Oral Vancomycin in a Manner Dependent on the Duration of Treatment

(A) Schematic of the treatment regimen utilized for each cohort in this study.

(B) Tail-immersion assay for mice receiving 5, 10, or 15 days of oral vancomycin (VAN, 10 mg/kg). Control subjects received 10 days of oral saline (SAL). Following morphine pellet (MP) implantation, the 10 day SAL and 5 day VAN cohorts demonstrated a progressive reduction in tail-flick latency and lacked a response to acute morphine challenge on day 5 (10 mg/kg, subcutaneously), indicating tolerance development. The 10 day VAN treatment resulted in a significant increase in tail-flick latency throughout the testing period (versus 10 day SAL) and an additional increase with acute morphine challenge on day 5, indicating tolerance prevention. This tolerance prevention was significantly enhanced with 15 day VAN treatment (versus 10 day VAN). 10 day SAL (N = 8), 5 day VAN (N = 10), 10 day VAN (N = 14), 15 day VAN (N = 10); significance indicated versus 10 day SAL (filled symbols, p < 0.05) and versus 10 day VAN (†p < 0.001, ‡p < 0.0001) by two-way repeated-measures ANOVA with Bonferroni post hoc analysis; data expressed as mean ± SEM (see Table S1 for additional values).