title: Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nunes
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Randall
authors.forename: Alexavier
authors.initials: A
authors.lastname: Estrada
authors.forename: Brian
authors.initials: B
authors.lastname: Epling
authors.forename: Evan E
authors.initials: EE
authors.lastname: Hart
authors.forename: Christie A
authors.initials: CA
authors.lastname: Lee
authors.forename: Younis
authors.initials: Y
authors.lastname: Baqi
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D053583:Interleukin-1beta / Q000008:administration & dosage*; D008297:Male; D009042:Motivation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D053583:Interleukin-1beta; C113602:MSX 3 compound; D043705:Receptor, Adenosine A2A; D011994:Recombinant Proteins; D014970:Xanthines