Neuron-Microglia Communication Delivered CRFR1 Phosphorylation during Long-Term Morphine Treatment

Morphine-mediated AC activation requires Src kinase, which was postulated to be responsible for morphine tolerance and dependence. Currently, we demonstrated that following long-term morphine treatment and subsequent naloxone precipitation, microglia was activated, which appeared to be obligatory for CD44 expression and production of IL-1beta, iNOS, MCP-1, MIP-1alpha, MIP-1beta, and TNF-alpha. Significantly, neuronal CRFR1 could be phosphorylated at serine 396 by c-Src-RSK1 signaling, which was subjected to microglia activation and preferentially strengthened AC5 up-regulation. Adding to this, it was revealed that RGS4 delivered signaling shift from MOR to CRFR1 and produced expression of somatic withdrawal signs and place conditioning but not antinociceptive tolerance. Then, the data indicated that desensitization of MOR appeared to under the control of neuron-microglia communication, the sensitized microglia served to maintain and potentiate morphine dependence and tolerance via brain CRFR1 receptor circuitry.