British journal of pharmacology
-
A large range of neuroadaptations develop in response to chronic opioid exposure and these are thought to be more or less critical for expression of the major features of opioid addiction: tolerance, withdrawal and processes that may contribute to compulsive use and relapse. This review considers these adaptations at different levels of organization in the nervous system including tolerance at the mu-opioid receptor itself, cellular tolerance and withdrawal in opioid-sensitive neurons, systems tolerance and withdrawal in opioid-sensitive nerve networks, as well as synaptic plasticity in opioid sensitive nerve networks. ⋯ The potential complexity of network, or systems adaptations that interact with opioid-sensitive neurons is great but some candidate neuropeptide systems that interact with mu-opioid sensitive neurons may play a role in tolerance and withdrawal, as might activation of glial signalling. Implication of synaptic forms of learning such as long term potentiation and long term depression in opioid addiction is still in its infancy but this ultimately has the potential to identify specific synapses that contribute to compulsive use and relapse.