Glial dysfunction in substance use disorders. New insights from PET and MR imaging

Alcohol and other drug pharmacology, including acute effects and mechanisms leading to drug seeking and addiction, has been extensively studied. Glial cells are critical for the proper development and function of the brain, and their reactivity is often an early signature of neurodegenerative and psychiatric disorders. Alcohol and other drugs have an impact on glial cells and promote a reactive glial state with cross-talk between neurons and glia. In this review, we summarize the major findings on the involvement of glial cells, particularly astrocytes, microglia and oligodendrocytes, in the effects of alcohol and other drugs on the brain. We focus on the contribution of imaging modalities, particularly Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), to understanding these mechanisms in the living brain. We analyze the role of glia in the cerebral effects of alcohol and other drugs through various ways including glutamate homeostasis, neuroinflammatory process, myelin and white matter integrity and blood-brain barrier permeability. A review of targets, radioligands, and methods used or needed in PET and MRI is presented and discussed. The analyze of PET and MRI studies confirms the need for more selective radioligands and more appropriate methods that selectively target different glial cell types.