Figure 3.

Increased basal analgesia in β-arr2-/- mice is reversed by μ receptor inverse agonists and unaffected by neutral antagonists. A. Using time to respond to tail withdrawal from 48°C water, β-arr2-/- mice showed a delayed withdrawal latency compared to β-arr2+/+ mice, (p < 0.05 β-arr2-/- vs β-arr2+/+). B. Naloxone (0.5 mg/kg), reduced the tail withdrawal latency when administered to β-arr2-/- mice 30 and 60 min after injection (#p < 0.05 vs untreated β-arr2-/-), but had no effect in β-arr2+/+ or β-arr2+/- mice. C, D and E. 6α- and 6β-naloxol, (1 mg and 10 mg/kg respectively) and the combination of 6α-naloxol (1 mg/kg) with naloxone (0.5 mg/kg), had no effect on the analgesic profile of the β-arr2-/- mice who continued to show an attenuated response compared with β-arr2+/+ mice (*p < 0.05, **p < 0.005 and ***p < 0.0001 vs β-arr2+/+). F. Similar to naloxone, naltrexone (0.5 mg/kg) reduced the increase in basal analgesia seen in β-arr2-/- mice to wild-type levels 30 min after the injection, but had no effect in β-arr2+/+ or β-arr2+/-mice. **p < 0.001 vs β-arr2+/+ and *p < 0.05 vs β-arr2+/-, #p < 0.05 vs untreated β-arr2-/- mice. G. In contrast, 6β-naltrexol (10 mg/kg) had no effect on the analgesic profile of β-arr2-/-, β-arr2+/-, or β-arr2+/+ mice. **p < 0.001 vs β-arr2+/+ and *p < 0.05 vs β-arr2+/+ mice