Potential of Glial Cell Modulators in the Management of Substance Use Disorders

The pervasive and devastating nature of substance use disorders underlies the need for the continued development of novel pharmacotherapies. We now know that glia play a much greater role in neuronal processes than once believed.  The various types of glial cells (e.g., astrocytes, microglial, oligodendrocytes) participate in numerous functions that are crucial to healthy central nervous system function. Drugs of abuse have been shown to interact with glia in ways that directly contribute to the pharmacodynamic effects responsible for their abuse potential. Through their effect upon glia, drugs of abuse also alter brain function resulting in behavioral changes associated with substance use disorders. Therefore, drug-induced changes in glia and inflammation within the central nervous system (neuroinflammation) have been investigated to treat various aspects of drug abuse and dependence. This article presents a brief overview of the effects of each of the major classes of addictive drugs on glia. Next, the paper reviews the pre-clinical and clinical studies assessing the effects that glial modulators have on abuse-related behavioral effects, such as pleasure, withdrawal, and motivation. There is a strong body of pre-clinical literature demonstrating the general effectiveness of several glia-modulating drugs in models of reward and relapse. Clinical studies have also yielded promising results, though not as robust. There is still much to disentangle regarding the integration between addictive drugs and glial cells. Improved understanding of the relationship between glia and the pathophysiology of drug abuse should allow for more precise exploration in the development and testing of glial-directed treatments for substance use disorders.