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DESPITE tremendous efforts in the search for safe, efficacious and non-addictive opioids for pain treatment, morphine remains the most valuable painkiller in contemporary medicine. Opioids exert their pharmacological actions through three opioid-receptor classes^1,2, µ, δ and κ, whose genes have been cloned³. Genetic approaches are now available to delineate the contribution of each receptor in opioid function in vivo. Here we disrupt the μ-opioid-receptor gene in mice by homologous recombination and find that there are no overt behavioural abnormalities or major compensatory changes within the opioid system in these animals. Investigation of the behavioural effects of morphine reveals that a lack of μ receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence. We observed no behavioural responses related to δ- or κ-receptor activation with morphine …