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BEHAVIORAL PHARMACOLOGY
-Arrestin 2 Knockout Mice
Departments of Pharmacology and Psychiatry, Ohio State University College of Medicine, Columbus, Ohio (K.M.R., L.M.B.); and Department of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina (J.K.L.W.)
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, 
-arrestin 2, display profoundly altered morphine responses. -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.
Address correspondence to: Laura M. Bohn, Departments of Pharmacology and Psychiatry, Ohio State University College of Medicine, 333 West 10th Avenue, 5184A Graves Hall, Columbus, OH 43210-1239. E-mail: bohn.24{at}osu.edu
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