Figure 6.

Decrease in NeuroD1 activity accounted for the different abilities of opioids to induce tolerance. (A–C) Mice were injected daily with 5 × ED₅₀ doses on day 1 (three times a day) from day 2 to day 9 and subjected to MWM tests beginning on day 29. The mice injected with morphine were divided into six groups; four groups of mice underwent MWM tests beginning on day 10, day 16, day 23, or day 29, whereas the other two groups of mice had 190-vir or nd-vir injection on day 10 and underwent MWMs test beginning on day 29 (A). The acquisition of contextual memory was summarized (B, C). (D–F) Mice injected with con-vir, nd-vir, 2× nd-vir, or 5× nd-vir on day 2 were used for experiments following the similar procedures in Figure 1A (D). The ED₅₀ values on day 11 and day 20 were summarized for morphine (E) and for fentanyl (F). Tolerance development was also summarized (G). One-way analysis of variance with Dunnett test as post hoc was used for comparisons between the basal level—day 1 (E, F) and con-vir (G)—and all other data in the same data set. Only significant differences were listed. ^*p < .05, ^**p < .01, ^***p < .001. Additional comparisons were performed between indicated lanes. MWM, Morris water maze; ns, not significant; other abbreviations as in Figure 1.