Addiction is a neuropsychiatric disorder characterized by uncontrolled drug use and heightened relapse susceptibility. While brain regions controlling multiple aspects of human behavior are known to be dysregulated by drugs of abuse, our limited understanding of the molecular and cellular regulation of neural circuits in the mammalian brain pose a fundamental barrier in establishing the etiology of drug addiction. Synaptic transmission has been a key form of intercellular signaling since the emergence of nervous systems. Evolution subsequently enriched this ancient form of signaling by accumulating new genes that dramatically increased the computational capacity of intercellular signaling. This included the recruitment of glial cells, particularly astrocytes, to the regulation of neural circuits encoding sophisticated behaviors. Here, we review the diverse ways in which bidirectional signaling between neurons and glial cells regulates complex brain function to demonstrate the potential for this poorly understood form of intercellular signaling to contribute to drug addiction.
