Toll-like receptor 3 dynamics in female C57BL/6J mice: Regulation of alcohol intake

Anna S. Warden, Moatasem Azzam, Adriana DaCosta, Sonia Mason, Yuri A. Blednov, Robert O Messing, R. Dayne Mayfield, R A Harris

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Although there are sex differences in the effects of alcohol on immune responses, it is unclear if sex differences in immune response can influence drinking behavior. Activation of toll-like receptor 3 (TLR3) by polyinosinic:polycytidylic acid (poly(I:C)) produced a rapid proinflammatory response in males that increased alcohol intake over time (Warden et al., 2019). Poly(I:C) produced a delayed and prolonged innate immune response in females. We hypothesized that the timecourse of innate immune activation could regulate drinking behavior in females. Therefore, we chose to test the effect of two time points in the innate immune activation timecourse on every-other-day two-bottle-choice drinking: (1) peak activation; (2) descending limb of activation. Poly(I:C) reduced ethanol consumption when alcohol access occurred during peak activation. Poly(I:C) did not change ethanol consumption when alcohol access occurred on the descending limb of activation. Decreased levels of MyD88-dependent pathway correlated with decreased alcohol intake and increased levels of TRIF-dependent pathway correlated with increased alcohol intake in females. To validate the effects of poly(I:C) were mediated through MyD88, we tested female mice lacking Myd88. Poly(I:C) did not change alcohol intake in Myd88 knockouts, indicating that poly(I:C)-induced changes in alcohol intake are dependent on MyD88 in females. We next determined if the innate immune timecourse also regulated drinking behavior in males. Poly(I:C) reduced ethanol consumption in males when alcohol was presented at peak activation. Therefore, the timecourse of innate immune activation regulates drinking behavior and sex-specific dynamics of innate immune response must be considered when designing therapeutics to treat excessive drinking.

Original languageEnglish (US)
Pages (from-to)66-76
Number of pages11
JournalBrain, Behavior, and Immunity
Volume77
DOIs
StatePublished - Mar 1 2019

Fingerprint

Toll-Like Receptor 3
Inbred C57BL Mouse
Alcohols
Drinking Behavior
Ethanol
Innate Immunity
Sex Characteristics
Alcohol Drinking
Drinking
Extremities
Poly I-C
polyriboinosinic-polyribocytidylic acid

Keywords

  • Alcohol
  • Alcohol use disorder
  • Cytokines
  • Drinking
  • Females
  • Neuroimmune
  • Poly(I:C)
  • Sex
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Toll-like receptor 3 dynamics in female C57BL/6J mice : Regulation of alcohol intake. / Warden, Anna S.; Azzam, Moatasem; DaCosta, Adriana; Mason, Sonia; Blednov, Yuri A.; Messing, Robert O; Mayfield, R. Dayne; Harris, R A.

In: Brain, Behavior, and Immunity, Vol. 77, 01.03.2019, p. 66-76.

Research output: Contribution to journalArticle

Warden, Anna S. ; Azzam, Moatasem ; DaCosta, Adriana ; Mason, Sonia ; Blednov, Yuri A. ; Messing, Robert O ; Mayfield, R. Dayne ; Harris, R A. / Toll-like receptor 3 dynamics in female C57BL/6J mice : Regulation of alcohol intake. In: Brain, Behavior, and Immunity. 2019 ; Vol. 77. pp. 66-76.
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