Understanding Microglia in Mesocorticolimbic Circuits: Implications for the Study of Chronic Stress and Substance Use Disorders. Cells 2025 Jul 02;14(13)
Date
07/11/2025Pubmed ID
40643534Pubmed Central ID
PMC12249056DOI
10.3390/cells14131014Scopus ID
2-s2.0-105010560797 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Exposure to chronic stress creates vulnerability to drug misuse and presents a barrier to sustained recovery for many individuals experiencing substance use disorders (SUDs). Preclinical literature demonstrates that stress modulates psychostimulant intake and seeking, yet there are wide gaps in our understanding of the specific mechanisms by which stress promotes brain changes that may govern addiction-related behaviors. Recent data suggest that microglia, innate immune cells in the central nervous system, are highly responsive to chronic stressors, and several mechanistic links have been explored highlighting the critical role microglia play in stress-related brain adaptation. Importantly, psychostimulants may engage similar microglial machinery, which opens the door for investigation into how microglia may be involved in shaping motivation for psychostimulants, especially in the context of stress exposure. The aims of this review are threefold: 1. Offer a brief overview of microglial biology in the adult brain. 2. Review current methods of interrogating microglial function with a focus on morphometric analyses. 3. Highlight preclinical research describing how microglia contribute to brain changes following chronic stress and/or psychostimulant exposure. Ultimately, this review serves to prime investigators studying the intersection of stress and SUDs to consider the relevant impacts of microglial actions.
Author List
Nowak DB, Taborda-Bejarano JP, Chaure FJ, Mantsch JR, Garcia-Keller CAuthors
Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinJohn Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBrain
Chronic Disease
Humans
Microglia
Stress, Psychological
Substance-Related Disorders
