A review on the reciprocal interactions between neuroinflammatory processes and substance use and misuse, with a focus on alcohol misuse

ABSTRACT

Background: The last decade has witnessed a surge of findings implicating neuroinflammatory processes as pivotal players in substance use disorders. The directionality of effects began with the expectation that the neuroinflammation associated with prolonged substance misuse contributes to long-term neuropathological consequences. As the literature grew, however, it became evident that the interactions between neuroinflammatory processes and alcohol and drug intake were reciprocal and part of a pernicious cycle in which disease-relevant signaling pathways contributed to an escalation of drug intake, provoking further inflammation-signaling and thereby exacerbating the neuropathological effects of drug misuse.

Objectives: The goal of this review and its associated special issue is to provide an overview of the emergent findings relevant to understanding these reciprocal interactions. The review highlights the importance of preclinical and clinical studies in testing and validation of immunotherapeutics as viable targets for curtailing substance use and misuse, with a focus on alcohol misuse.

Methods: A narrative review of the literature on drug and neuroinflammation was conducted, as well as articles published in this Special Issue on Alcohol- and Drug-induced Neuroinflammation: Insights from Pre-clinical Models and Clinical Research.

Results: We argue that (a) demographic variables and genetic background contribute unique sensitivity to drug-related neuroinflammation; (b) co-morbidities between substance use disorders and affect dysfunction may share common inflammation-related signatures that predict the efficacy of immunotherapeutic drugs; and (c) examination of polydrug interactions with neuroinflammation is a critical area where greater research emphasis is needed.

Conclusions: This review provides an accessible and example-driven review of the relationship between drug misuse, neuroinflammatory processes, and their resultant neuropathological outcomes.

KEYWORDS:

• Neuroinflammation
• substance misuse
• immunotherapeutics
• review

Disclosure statement

No potential conflict of interest was reported by the author(s).

Contributors

Conceptualization, Visualization, Writing, Original draft preparation: Terrence Deak, Anny Gano, Ricardo Pautassi. Funding acquisition: Ricardo Pautassi. Data curation, Project administration, Investigation: Anny Gano, Ricardo Pautassi. Project administration, Resources: Anny Gano, Ricardo Pautassi. Writing, Original draft preparation, Resources: Terrence Deak, Anny Gano, Ricardo Pautassi

Additional information

Funding

This work was supported by the Center for Development and Behavioral Neuroscience (CDBN) at Binghamton University, NIH [Grant P50AA017823 to TD, and PICT-2019- 00180 and PICT-2018-00597] of FONCyT-Argentina to RMP. The funding agencies had no further role in study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.