Table 3.
Opioid analgesia in wild-type and exon 11 knockout mice
Drug | ED50, mg/kg (s.c.) |
Fold shift | P | ||
---|---|---|---|---|---|
Wild type (+/+) | Heterozygote (+/−) | Homozygote (−/−) | |||
Morphine | 1.58 ± 0.17 | 1.30 ± 0.20 | 2.58 ± 0.52 | 1.6 | 0.07 |
Methadone | 1.53 ± 0.06 | 1.56 ± 0.08 | 1.8 ± 0.14 | 1.2 | 0.11 |
M6G | 0.92 ± 0.12 | 0.97 ± 0.25 | 19.3 ± 4.2 | 21 | 0.0005 |
Heroin | 0.58 ± 0.11 | 0.48 ± 0.05 | 3.2 ± 0.8 | 5.5 | 0.0005 |
Fentanyl | 0.024 ± 0.002 | 0.020 ± 0.001 | 0.23 ± 0.09 | 9.7 | 0.024 |
Analgesia was assessed in cumulative dose–response studies with at least 8 animals/groups using the radiant heat tail-flick assay and was defined quantally as a doubling or greater of the baseline latency with a maximal latency of 10 sec to minimize tissue damage, as previously described (28). ED50 values were determined using probit analysis. Results are the means ± SEM of the ED50 values determined from independent dose–response studies for morphine (n = 5), methadone (n = 5), heroin (n = 7), M6G (n = 7), and fentanyl (n = 4). Differences among groups for each drug were determined by ANOVA.