Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization

Samantha E. Yohn, Yumna Arif, Allison Haley, Guiseppe Tripodi, Younis Baqi, Christa E. Müller, Noemi San Miguel, Mercè Correa, John D. Salamone*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


Rationale: Motivational dysfunctions such as anergia, fatigue, and reduced effort expenditure are common in patients with depression and other disorders. Pro-inflammatory cytokines are implicated in depression, and cytokine administration induces motivational deficits in humans. Objectives: These studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making. Methods: Rats were assessed using the concurrent fixed ratio 5-lever pressing/chow feeding choice procedure, which measures the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (lab chow). Results: IL-6 (2.0–8.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing chow intake. Further experiments showed that the adenosine A2A antagonist MSX-3 and the stimulant methylphenidate attenuated the effort-related impairments produced by IL-6, increasing lever pressing and decreasing chow intake in IL-6 treated rats. The same doses of IL-6 did not alter food intake or preference in parallel free-feeding choice studies, demonstrating that these low doses were not altering preference for the high carbohydrate pellets or generally suppressing appetite. Also, IL-6 did not affect body temperature. Microdialysis studies showed that 8.0 μg/kg IL-6 significantly decreased extracellular dopamine in nucleus accumbens core. Conclusions: In summary, IL-6 reduces the tendency to work for food, even at low doses that do not produce fever or loss of appetite. Dopaminergic mechanisms may be involved in these effort-related effects. This research has implications for the involvement of cytokines in motivational dysfunctions such as anergia and fatigue.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
Publication statusAccepted/In press - Aug 6 2016


  • Accumbens
  • Anergia
  • Depression
  • Dopamine
  • Fatigue
  • Motivation

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology


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