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The existing evidence is primarily derived from preclinical models or short-term human trials, which limits the generalizability of findings to diverse populations with varying degrees of depression severity
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While it is clear that arrestin-dependent internalization can sequester the opioid receptors in compartments that reduce the efficiencies of certain forms of signaling (e.g., G βγ activation of Kir3 channels), it is now equally clear that arrestin binding does not inactivate all receptor signaling
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