TY - JOUR T1 - Morphine Side Effects in β-Arrestin 2 Knockout Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1195 LP - 1201 DO - 10.1124/jpet.105.087254 VL - 314 IS - 3 AU - Kirsten M. Raehal AU - Julia K. L. Walker AU - Laura M. Bohn Y1 - 2005/09/01 UR - http://jpet.aspetjournals.org/content/314/3/1195.abstract N2 - Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. Pharmacological approaches taken to preserve the analgesic properties, while eliminating the unwanted side effects, have met with very limited success. Here, we provide evidence that altering μ opioid receptor regulation may provide a novel approach to discriminate morphine's beneficial and deleterious effects in vivo. We have previously reported that mice lacking the G protein-coupled receptor regulatory protein, β-arrestin 2, display profoundly altered morphine responses. β-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. In this report, we examine whether the side effects of morphine treatment are also augmented in this animal model. Surprisingly, the genetic disruption of opioid receptor regulation, while enhancing and prolonging analgesia, dramatically attenuates the respiratory suppression and acute constipation caused by morphine. The American Society for Pharmacology and Experimental Therapeutics ER -