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

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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
JournalPsychopharmacology
DOIs
Publication statusAccepted/In press - Aug 6 2016

Fingerprint

Interleukin-6
Pharmacology
Cytokines
Appetite
Fatigue
Carbohydrates
Choice Behavior
Depression
Food Preferences
Food
Methylphenidate
Microdialysis
Nucleus Accumbens
Health Expenditures
Body Temperature
Adenosine
Dopamine
Decision Making
Fever
Eating

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6 : pharmacological and neurochemical characterization. / Yohn, Samantha E.; Arif, Yumna; Haley, Allison; Tripodi, Guiseppe; Baqi, Younis; Müller, Christa E.; Miguel, Noemi San; Correa, Mercè; Salamone, John D.

In: Psychopharmacology, 06.08.2016, p. 1-12.

Research output: Contribution to journalArticle

Yohn, Samantha E. ; Arif, Yumna ; Haley, Allison ; Tripodi, Guiseppe ; Baqi, Younis ; Müller, Christa E. ; Miguel, Noemi San ; Correa, Mercè ; Salamone, John D. / Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6 : pharmacological and neurochemical characterization. In: Psychopharmacology. 2016 ; pp. 1-12.
@article{346273a8b0d64bed86078cda45fe0468,
title = "Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization",
abstract = "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.",
keywords = "Accumbens, Anergia, Depression, Dopamine, Fatigue, Motivation",
author = "Yohn, {Samantha E.} and Yumna Arif and Allison Haley and Guiseppe Tripodi and Younis Baqi and M{\"u}ller, {Christa E.} and Miguel, {Noemi San} and Merc{\`e} Correa and Salamone, {John D.}",
year = "2016",
month = "8",
day = "6",
doi = "10.1007/s00213-016-4392-9",
language = "English",
pages = "1--12",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6

T2 - pharmacological and neurochemical characterization

AU - Yohn, Samantha E.

AU - Arif, Yumna

AU - Haley, Allison

AU - Tripodi, Guiseppe

AU - Baqi, Younis

AU - Müller, Christa E.

AU - Miguel, Noemi San

AU - Correa, Mercè

AU - Salamone, John D.

PY - 2016/8/6

Y1 - 2016/8/6

N2 - 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.

AB - 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.

KW - Accumbens

KW - Anergia

KW - Depression

KW - Dopamine

KW - Fatigue

KW - Motivation

UR - http://www.scopus.com/inward/record.url?scp=84982984227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84982984227&partnerID=8YFLogxK

U2 - 10.1007/s00213-016-4392-9

DO - 10.1007/s00213-016-4392-9

M3 - Article

SP - 1

EP - 12

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

ER -