Opioid use disorder (OUD) is a chronic relapsing disorder that, whilst initially driven by
activation of brain reward neurocircuits, increasingly engages anti-reward neurocircuits that …

G protein-coupled receptors (GPCRs) are the largest class of receptors in the human
genome and some of the most common drug targets. It is now well established that GPCRs …

Morphine and fentanyl are among the most used opioid drugs that confer analgesia and
unwanted side effects through both G protein and arrestin signaling pathways of μ-opioid …

Drugs targeting the μ-opioid receptor (μOR) are the most effective analgesics available but
are also associated with fatal respiratory depression through a pathway that remains …

Anhedonia is the inability to experience pleasure from rewarding or enjoyable activities and
is a core symptom of depression in humans. Here, we describe a protocol for the …

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side
effects of morphine and related opioids—which include fatal respiratory depression—are …

Biased agonism has been proposed as a means to separate desirable and adverse drug
responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe …

Activation of the μ-opioid receptor (μOR) is responsible for the efficacy of the most effective
analgesics. To shed light on the structural basis for μOR activation, here we report a 2.1 Å X …

The visual/β-arrestins, a small family of proteins originally described for their role in the
desensitization and intracellular trafficking of G protein–coupled receptors (GPCRs), have …

Background and Purpose GPCRs can signal through both G proteins and β‐arrestin2. For
the μ‐opioid receptor, early experimental evidence from a single study suggested that G …