Glial modulators: a novel pharmacological approach to altering the behavioral effects of abused substances

Commonly abused drugs including opioids, stimulants and alcohol activate glia cells, an effect that has been identified across species. Glia, specifically astrocytes and microglia, have been shown to contribute directly to behaviors predictive of the abuse liability of these drugs. Although still in its infancy, research investigating the effects of pharmacological modulation of glial activity on these behaviors has provided encouraging findings suggesting glial cell modulators as potential pharmacotherapies for substance-use disorders.

This review first explores the evidence establishing glial-mediated modulations of behaviors associated with opioid, stimulant and alcohol exposure, with emphasis placed on the neuroanatomical substrates for these effects. Next, neurobiological and behavioral studies evaluating the ability of glial cell modulators to prevent and reverse the effects of these abused substances will be considered. Finally, the potential clinical efficacy of glial cell modulators as a novel pharmacological approach to treat substance-use disorders in relation to currently available, conventional pharmacotherapies will be discussed.

Though the relationship between drug-induced glial activity and behaviors indicative of drug abuse and dependence is not yet fully elucidated, the evidence for the association continues to grow. The use of glial modulators as pharmacological tools to investigate this relationship has also yielded findings supporting their potential clinical efficacy for treating substance-use disorders.