Mice without the arrestin-3 gene (Arr3-KO) were reported to show increased analgesia (Bohn et al., 1999), reduced tolerance (Bohn et al., 2000), and reduced respiratory depression and constipation (Raehal et al., 2005) in response to morphine compared to wild type (WT) mice. This evidence concerns the gene ARR3 and Respiratory insufficiency due to muscle weakness.