Figure 4.

A single administration of the σ1 receptor antagonist restores morphine analgesia in opioid‐tolerant mice. (a) After a 14‐day treatment with morphine (2.5 mg·kg⁻¹, twice a day during 14 days), mice received acute administrations of morphine (2.5 mg·kg⁻¹), E‐52862 (5–20 mg·kg⁻¹), or combinations of both drugs. (b–d) Mice repeatedly treated with the opioid developed analgesic tolerance. (b) The antinociceptive effect of morphine was not recovered for at least 9 days after the end of the repeated treatment. Single sub‐effective (5 mg·kg⁻¹) (c) and effective doses (20 mg·kg⁻¹) (d) of E‐52862 combined with morphine produced a restoration of opioid analgesia in morphine‐tolerant mice. Mechanical thresholds expressed as mean ± SEM. The number of animals is the following (first value represents sham groups and second value represents MIA groups): (b) 8, 8; (c) 8, 8; and (d) 8, 10. *P<.05, significant difference between MIA‐POST and Sham‐POST; #P<.05, significant difference between MIA‐PRE and Sham‐PRE; +P<.05, significant difference between MIA‐PRE and MIA‐POST; †P<.05, significant difference between MIA‐POST and MIA‐POST at Day 1 (three‐way repeated‐measures ANOVA plus Fisher least significant difference test). MIA, monoiodoacetate