title: Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization.
abstract: 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.
  
  
  
  These studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors: Samantha E
authors: SE
authors: Yohn
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors: Yumna
authors: Y
authors: Arif
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors: Allison
authors: A
authors: Haley
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors: Guiseppe
authors: G
authors: Tripodi
authors: Universität Bonn, Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Bonn, Germany.|Department of Chemistry, Sultan Qaboos University, Muscat, Oman.
authors: Younis
authors: Y
authors: Baqi
authors: Universität Bonn, Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Bonn, Germany.
authors: Christa E
authors: CE
authors: Müller
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.|Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071, Castelló, Spain.
authors: Noemi San
authors: NS
authors: Miguel
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA.|Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071, Castelló, Spain.
authors: Mercè
authors: M
authors: Correa
authors: Department of Psychological Sciences, University of Connecticut, Storrs, CT, 06269-1020, USA. john.salamone@uconn.edu.
authors: John D
authors: JD
authors: Salamone
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects*; D016207:Cytokines; D003657:Decision Making / Q000187:drug effects; D003863:Depression; D004298:Dopamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D017551:Microdialysis; D009042:Motivation / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D016207:Cytokines; D015850:Interleukin-6; C113602:MSX 3 compound; D014970:Xanthines; D008774:Methylphenidate; D004298:Dopamine
keywords: Accumbens; Anergia; Depression; Dopamine; Fatigue; Motivation