Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.
Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction.
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO 80309-0345, USA. matt.frank@colorado.edu
Matthew G
MG
Frank
Linda R
LR
Watkins
Steven F
SF
Maier
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology* / Q000523:psychology; D004660:Encephalitis / Q000276:immunology* / Q000523:psychology; D005938:Glucocorticoids; D007113:Immunity, Innate / Q000276:immunology; D015213:Neuroimmunomodulation; D051381:Rats; D013312:Stress, Physiological / Q000276:immunology*; D013315:Stress, Psychological / Q000276:immunology* / Q000523:psychology; D019966:Substance-Related Disorders / Q000276:immunology* / Q000523:psychology
D005938:Glucocorticoids
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