ArticlePsychopharmacology2016
Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 94 citations in OpenAlex.
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- Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.Brain, behavior, and immunity · 2025Trial
- Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study.Molecular psychiatry · 2022Trial
- Neurochemical drivers of effort: The roles of dopamine and beyond in physical and cognitive exertion.Neuroscience and biobehavioral reviews · 2026Review
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Inflammatory models of depression in rodents and humans.Frontiers in psychiatry · 2026Review
- Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Advancing an Inflammatory Subtype of Major Depression.The American journal of psychiatry · 2025Review
- A neuroimmune circuit mediates cancer cachexia-associated apathy.Science (New York, N.Y.) · 2025Article
- Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a non-human primate model of cytokine-Induced depression.Brain, behavior, and immunity · 2025Article
- Treatment-resistant depression: molecular mechanisms and management.Molecular biomedicine · 2024Review
- Glycolytic metabolism: Food for immune cells, fuel for depression?Brain, behavior, & immunity - health · 2024Article
- From movement to motivation: a proposed framework to understand the antidepressant effect of exercise.Translational psychiatry · 2024Review
- Inflammation as a Potential Mechanism Contributing to Sexual Functioning Following Initiation of Gender-Affirming Hormone Therapy.Current sexual health reports · 2024Article
- Annual Research Review: Neuroimmune network model of depression: a developmental perspective.Journal of child psychology and psychiatry, and allied disciplines · 2024Review
- Article
- Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models.Neuroscience and biobehavioral reviews · 2023Review
- Chronic lipopolysaccharide impairs motivation when delivered to the ventricles, but not when delivered peripherally in male rats.Physiology & behavior · 2022Article
- Cellular and immunometabolic mechanisms of inflammation in depression: Preliminary findings from single cell RNA sequencing and a tribute to Bruce McEwen.Neurobiology of stress · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleMotivational 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.
objectivesThese studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.
methodsRats 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).
resultsIL-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.
conclusionsIn 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.