Role of μ-opioid system in the formation of memory of placebo responses

The endogenous opioid system is centrally involved in short-term placebo analgesic effects, but its potential regulation of memory and learning circuits, critical for the sustainability of placebo responses, has not been explored. Here we examined the recall of analgesic effects after placebo administration as a function of its initial capacity to activate μ-opioid neurotransmission. Memories of therapeutic/adverse responses 24 hours after placebo administration were associated with differences in μ-opioid neurotransmission in the Papez circuit, VTA, amygdala and septum. These data suggests that μ-opioid neurotransmission is involved in the recall of therapeutic benefit, providing a framework to understand stimulus learning and long-term therapeutic effect associations.