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. 2002 Dec 20;100(1):271–276. doi: 10.1073/pnas.0136822100

Figure 2.

Figure 2

Effects of the GIRK2-null mutation on morphine antinociception in male and female mice. Between 14 and 19 mice per group were tested. All mice received all of the doses in a randomized order, with a 1-week interval between treatments. (a) Morphine dose–response curve generated with tail-flick test (legend is the same as in b). (b) Comparison of areas under the morphine dose-response curves for WT males, WT females, mutant males, and mutant females. One-way ANOVA (F3,64 = 31.55) followed by Bonferroni post test indicated a significant difference between male and female WT animals in response to morphine (*, P < 0.05). The GIRK2-null mutation decreased antinociceptive effectiveness of morphine in both male and female mice (#, P < 0.001, compared with either male or female WT mice). At the same time, the sex difference present in WT mice was eliminated by the null mutation of the GIRK2 gene. (c) Morphine dose–response curves generated in the hot plate test. (d) Comparison of areas under the dose–response curves for WT males, WT females, mutant males, and mutant females. One-way ANOVA (F3,62 = 35.99) followed by Bonferroni post test indicated the same morphine response profile as the one in the tail-flick test: (i) sex difference in WT animals (*, P < 0.001) disappeared in mutant mice; (ii) morphine antinociceptive effectiveness in male and female mutant mice was decreased relative to either male or female WT animals (#, P < 0.001). (e) Effects of morphine on pain-related behaviors elicited by injection of 5% formalin (between five and nine animals per group; because there were no sex differences in the baseline test, male and female animals in the baseline group were combined). Both 3.0 and 10 mg/kg morphine inhibited formalin-elicited first-phase (0–5 min) behaviors (*, P < 0.001, compared with the baseline). The 10 mg/kg dose had a greater antinociceptive effect in WT mice ($, P < 0.001, compared with the effects observed in mutant mice). Both doses of morphine eliminated the effects of the GIRK2-null mutation in the interphase (5–15 min; *, P < 0.001). The 3.0 mg/kg dose of morphine reduced and the 10 mg/kg dose eliminated the second phase (15–40 min) of responses (#, P < 0.05 and *, P < 0.001, compared with the baseline).