Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task

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• 作者：Eric J. Nunes (1)
  Patrick A. Randall (1)
  Alexavier Estrada (1)
  Brian Epling (1)
  Evan E. Hart (1)
  Christie A. Lee (1)
  Younis Baqi (2)
  Christa E. Müller (2)
  Mercè Correa (1) (3)
  John D. Salamone (1)
  
• 关键词：Accumbens ; Motivation ; Fatigue ; Depression ; Anergia ; Adenosine
• 刊名：Psychopharmacology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：231
• 期：4
• 页码：727-736
• 全文大小：564 KB
• 作者单位：Eric J. Nunes (1)
  Patrick A. Randall (1)
  Alexavier Estrada (1)
  Brian Epling (1)
  Evan E. Hart (1)
  Christie A. Lee (1)
  Younis Baqi (2)
  Christa E. Müller (2)
  Mercè Correa (1) (3)
  John D. Salamone (1)
  
  1. Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA
  2. Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Universit?t Bonn, Bonn, Germany
  3. àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071, Castelló, Spain
  
• ISSN：1432-2072

文摘

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-.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.