Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta

Studies with the concurrent fixed ratio 5/ chow feeding choice task

Eric J. Nunes, Patrick Arthur Randall, Alexavier Estrada, Brian Epling, Evan E. Hart, Christie A. Lee, Younis Baqi, Christa E. Müller, Mercè Correa, John D. Salamone

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

Original languageEnglish (US)
Pages (from-to)727-736
Number of pages10
JournalPsychopharmacology
Volume231
Issue number4
DOIs
StatePublished - Feb 1 2014

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Interleukin-1beta
Cohort Studies
Cytokines
Choice Behavior
Appetite
Fatigue
Carbohydrates
Depression
Food Preferences
Food
Aptitude
Body Temperature
Research
Adenosine
Esters
Salts
Eating

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nunes, Eric J. ; Randall, Patrick Arthur ; Estrada, Alexavier ; Epling, Brian ; Hart, Evan E. ; Lee, Christie A. ; Baqi, Younis ; Müller, Christa E. ; Correa, Mercè ; Salamone, John D. / Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta : Studies with the concurrent fixed ratio 5/ chow feeding choice task. In: Psychopharmacology. 2014 ; Vol. 231, No. 4. pp. 727-736.
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abstract = "Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.",
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Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta : Studies with the concurrent fixed ratio 5/ chow feeding choice task. / Nunes, Eric J.; Randall, Patrick Arthur; Estrada, Alexavier; Epling, Brian; Hart, Evan E.; Lee, Christie A.; Baqi, Younis; Müller, Christa E.; Correa, Mercè; Salamone, John D.

In: Psychopharmacology, Vol. 231, No. 4, 01.02.2014, p. 727-736.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta

T2 - Studies with the concurrent fixed ratio 5/ chow feeding choice task

AU - Nunes, Eric J.

AU - Randall, Patrick Arthur

AU - Estrada, Alexavier

AU - Epling, Brian

AU - Hart, Evan E.

AU - Lee, Christie A.

AU - Baqi, Younis

AU - Müller, Christa E.

AU - Correa, Mercè

AU - Salamone, John D.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

AB - Rationale: Effort-related motivational symptoms such as anergia and fatigue are common in patients with depression and other disorders. Research implicates pro-inflammatory cytokines in depression, and administration of cytokines can induce effort-related motivational symptoms in humans. Objectives: The present experiments focused on the effects of the pro-inflammatory cytokine interleukin 1-beta (IL-1β) on effort-related choice behavior. Methods: Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure, which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (laboratory chow). Results: IL-1β (1.0-4.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing intake of the freely available chow. The second experiment assessed the ability of the adenosine A2A antagonist (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl-2,6-dioxo-1-prop-2-ynyl-1,2,6, 7-tetrahydropurin-3-yl] propyl] ester disodium salt (MSX-3) to reverse the behavioral effects of IL-1β. MSX-3 attenuated the effort-related impairments produced by IL-1β, increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1β did not alter food intake or preference in parallel free-feeding choice studies, indicating that these low doses were not generally suppressing appetite or altering preference for the high carbohydrate pellets. In addition, IL-1β did not affect core body temperature. Conclusions: These results indicate that IL-1β can reduce the tendency to work for food, even at low doses that do not produce a general sickness, malaise, or loss of appetite. This research has implications for the involvement of cytokines in motivational symptoms such as anergia and fatigue.

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