Morphine side effects in β-arrestin 2 knockout mice

KM Raehal, JKL Walker, LM Bohn - Journal of Pharmacology and …, 2005 - ASPET
KM Raehal, JKL Walker, LM Bohn
Journal of Pharmacology and Experimental Therapeutics, 2005ASPET
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 …
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.
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