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Review
. 2017 Nov 1:180:156-170.
doi: 10.1016/j.drugalcdep.2017.08.003. Epub 2017 Aug 31.

Glial and neuroinflammatory targets for treating substance use disorders

Ryan K Bachtell  1 , Jermaine D Jones  2 , Keith G Heinzerling  3 , Patrick M Beardsley  4 , Sandra D Comer  5
Affiliations
Review

Glial and neuroinflammatory targets for treating substance use disorders

Ryan K Bachtell et al. Drug Alcohol Depend. .

Abstract

Background: The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders. Consequently, drug-induced changes in glia-driven processes in the brain represent potential targets for pharmacotherapeutics treating substance use disorders.

Methods: Four speakers presented preclinical and clinical research illustrating the effects that glial modulators have on abuse-related behavioral effects of psychostimulants and opioids. This review highlights some of these findings and expands its focus to include other research focused on drug-induced glia abnormalities and glia-focused treatment approaches in substance use disorders.

Results: Preclinical findings show that drugs of abuse induce neuroinflammatory signals and disrupt glutamate homeostasis through their interaction with microglia and astrocytes. Preclinical and clinical studies testing the effects of glial modulators show general effectiveness in reducing behaviors associated with substance use disorders.

Conclusions: The contribution of drug-induced glial activity continues to emerge as an intriguing target for substance use disorder treatments. Clinical investigations of glial modulators have yielded promising results on substance use measures and indicate that they are generally safe and well-tolerated. However, results have not been entirely positive and more questions remain for continued exploration in the development and testing of glial-directed treatments for substance use disorders.

Keywords: Alcohol; Astrocyte; Cocaine; Cytokine; Glutamate; Inflammatory; Innate immune; Microglia; Morphine; Opioid; Psychostimulant.

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Conflict of interest statement

Conflicts of Interest

RKB and PMB have no conflicts of interest to declare. JDJ, KGH and SDC were provided provided with ibudilast by Medicinova. Supplemental funding was provided to JDJ and SDC by Medicinova for P50DA09236 and U54DA037842. JDJ and SDC were provided with pioglita-zone by Omeros Corporation (R01DA031022).

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MeSH terms

Substances