Figure 3.

Effect of physiological β-End 1–31 derivatives on morphine and β-End 1–31 analgesia. Implication of σ1Rs. (A) The mice were icv-injected with 25 nmol of β-End 1–26, β-End 1–27 and ^αN-acetylated derivatives 20 min before icv 0.5 nmol β-End 1–31. Analgesia was determined at the indicated postinjection intervals. (B) CD1 wild-type and σ1R^−/− mice were administered C terminal peptide sequences 27–31, 28–31 and 30–31 of β-End 1–31 through an icv injection 20 min before 0.5 nmol of the whole β-End 1–31 and morphine (10 nmols) were injected icv. The σ1R agonist PPCC, 3 nmol icv, was administered 10 min before β-End C-terminal peptides. * Indicates that at the corresponding time interval, the ligand being evaluated significantly altered β-End 1–31 or morphine analgesia. (C) A series of exogenous σ1R ligands (3 nmol) were icv-injected 20 min before 0.5 nmol β-End 1–31 was administered via icv in wild-type mice. The σ1R antagonist S1RA was also icv-injected before β-End 1–31 was administered icv in σ1R^−/− mice. (D) The effects of several doses of S1RA on morphine analgesia were studied in wild-type and σ1R^−/− mice. (E) A series of σ1R ligands were icv-injected 20 min before different opioids, and analgesia was evaluated 30 min after β-End 1–31 (0.5 nmol, icv), 15 min after DAMGO (0.1 nmol, icv), DPDPE (10 nmol, icv) and D-Ala²-deltorphin II (10 nmol, icv). (A–E) Bars are the mean ± SD of the pooled data from six mice. * Indicates that at the corresponding time interval, the ligand being evaluated significantly altered control analgesia (grey bars). ϕ Significant difference with respect to the group treated with the opioid and S1RA. ANOVA followed by the Holm–Sidak multiple comparisons test, p < 0.05, 1-β > 0.80.