[Opioid receptor knockout mice]

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Context:

• Opioid receptors (mu, delta, kappa) are key targets for opiate drugs, influencing analgesia, reward, and physiological functions.
• Gene-targeting technology enables the creation of opioid receptor knockout mice, serving as vital models for in vivo studies.
• Understanding opioid receptor function is crucial for developing novel therapeutic strategies and managing opiate-related effects.

Purpose:

• To elucidate the in vivo functions of mu, delta, and kappa opioid receptors using knockout mouse models.
• To investigate the specific roles of the mu-opioid receptor in mediating the therapeutic and adverse effects of morphine.
• To explore the involvement of the mu-opioid receptor in reward pathways and its interaction with other neurotransmitter systems.

Summary:

• Mice lacking the mu-opioid receptor exhibit a paradoxical decrease in thermal nociception but an increased threshold for visceral stimuli.
• Absence of the mu receptor in mice abolishes morphine-induced analgesia, reward, respiratory depression, constipation, immunosuppression, and physical dependence.
• Mu-opioid receptor expression is essential for the analgesic effects mediated by delta and kappa receptors, and for cocaine and ethanol reward.

Impact:

• The mu-opioid receptor is identified as the primary molecular target for most of morphine's effects, both beneficial and detrimental.
• These findings underscore the critical role of the mu-opioid receptor in mediating analgesia, reward, and physiological responses to opiates.
• Mu-opioid receptor knockout mice provide an indispensable tool for dissecting complex interactions within the endogenous opioid and dopamine systems, paving the way for new drug development.