Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase

Elisabeth G. Vichaya, Geoffroy Laumet, Diana L. Christian, Aaron Grossberg, Darlene J. Estrada, Cobi J. Heijnen, Annemieke Kavelaars, Robert Dantzer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Despite years of research, our understanding of the mechanisms by which inflammation induces depression is still limited. As clinical data points to a strong association between depression and motivational alterations, we sought to (1) characterize the motivational changes that are associated with inflammation in mice, and (2) determine if they depend on inflammation-induced activation of indoleamine 2,3 dioxygenase-1 (IDO1). Lipopolysaccharide (LPS)-treated or spared nerve injured (SNI) wild type (WT) and Ido1−/− mice underwent behavioral tests of antidepressant activity (e.g., forced swim test) and motivated behavior, including assessment of (1) reward expectancy using a food-related anticipatory activity task, (2) willingness to work for reward using a progressive ratio schedule of food reinforcement, (3) effort allocation using a concurrent choice task, and (4) ability to associate environmental cues with reward using conditioned place preference. LPS- and SNI-induced deficits in behavioral tests of antidepressant activity in WT but not Ido1−/− mice. Further, LPS decreased food related-anticipatory activity, reduced performance in the progressive ratio task, and shifted effort toward the preferred reward in the concurrent choice task. These effects were observed in both WT and Ido1−/− mice. Finally, SNI mice developed a conditioned place preference based on relief from pain in an IDO1-independent manner. These findings demonstrate that the motivational effects of inflammation do not require IDO1. Further, they indicate that the motivational component of inflammation-induced depression is mechanistically distinct from that measured by behavioral tests of antidepressant activity.

Original languageEnglish (US)
Pages (from-to)364-371
Number of pages8
JournalNeuropsychopharmacology
Volume44
Issue number2
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Reward
Depression
Inflammation
Antidepressive Agents
Lipopolysaccharides
Food
Reinforcement Schedule
Aptitude
Cues
Pain
Research
Behavior Rating Scale

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase. / Vichaya, Elisabeth G.; Laumet, Geoffroy; Christian, Diana L.; Grossberg, Aaron; Estrada, Darlene J.; Heijnen, Cobi J.; Kavelaars, Annemieke; Dantzer, Robert.

In: Neuropsychopharmacology, Vol. 44, No. 2, 01.01.2019, p. 364-371.

Research output: Contribution to journalArticle

Vichaya, Elisabeth G. ; Laumet, Geoffroy ; Christian, Diana L. ; Grossberg, Aaron ; Estrada, Darlene J. ; Heijnen, Cobi J. ; Kavelaars, Annemieke ; Dantzer, Robert. / Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase. In: Neuropsychopharmacology. 2019 ; Vol. 44, No. 2. pp. 364-371.
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