Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior

Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid metabolites at TLR4 receptors, that are located primarily on microglia but are also present on astrocytes. Specifically, the M3G metabolite, which has no affinity for opioid receptors, exerts off-target effects on TLR4 receptors that can trigger downstream immunologic consequences. This off-target microglial reactivity, and the subsequent increase in microglial release of TNF alpha, IL-1 beta, and BDNF, have been suggested to modulate both opioid-induced reward and opioid-induced analgesia. Despite occurring indepen-dently of each other, these neuro-immune effects could converge and result in overactivation of the insula. This would produce an imbalance between the impulsive system and the executive system, such that the impulsive system's influence over behavior becomes dominant. This state, derived from changes in microglial reactivity, could contribute to impairment in a range of neurocognitive domains that are intricately involved in addiction and lead to increases in addiction-related behaviors.

Automated summary

Opioid-induced microglia reactivity can affect opioid reward and analgesic processes, leading to neurocognitive impairment in opioid addicted individuals. These effects are mediated by opioid metabolites acting on TLR4 receptors, resulting in increased release of inflammatory molecules. The resulting imbalance between the impulsive and executive systems may contribute to addiction-related behaviors.