Why is neuroimmunopharmacology crucial for the future of addiction research?

• Central immune signaling contributes significantly to drug reward.
• Toll-like receptor 4 signaling contributes to drug reward behaviors.
• Targeting central immune signaling may lead to future drug addiction interventions.

A major development in drug addiction research in recent years has been the discovery that immune signaling within the central nervous system contributes significantly to mesolimbic dopamine reward signaling induced by drugs of abuse, and hence is involved in the presentation of reward behaviors. Additionally, in the case of opioids, these hypotheses have advanced through to the discovery of the novel site of opioid action at the innate immune pattern recognition receptor Toll-like receptor 4 as the necessary triggering event that engages this reward facilitating central immune signaling. Thus, the hypothesis of major proinflammatory contributions to drug abuse was born. This review will examine these key discoveries, but also address several key lingering questions of how central immune signaling is able to contribute in this fashion to the pharmacodynamics of drugs of abuse. It is hoped that by combining the collective wisdom of neuroscience, immunology and pharmacology, into Neuroimmunopharmacology, we may more fully understanding the neuronal and immune complexities of how drugs of abuse, such as opioids, create their rewarding and addiction states. Such discoveries will point us in the direction such that one day soon we might successfully intervene to successfully treat drug addiction.This article is part of a Special Issue entitled ‘NIDA 40th Anniversary Issue’.