In vitro, you get different responses when you ramp up to a concentration, vs start at that concentration. This makes sense because the receptor internalizes after binding, so early exposure to low concentration reduces receptors available during the high concentration exposure.
This might translate into lower RD incidence in response to a robust time-release opioid, for the same reason.
I think there are short time-scale desensitization processes independent of this receptor internalization business as well.
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