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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

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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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Acknowledgments

This work was supported by a grant to J.S. from the National Institute of Mental Health (MH094966), and to Merce Correa from Fundació Bancaixa/U. Jaume I. (P1.1B2010-43), and a SURF grant to B. Epling.

Disclosure/conflict of interest

J. Salamone has received grants from Merck-Serrono, Pfizer, and Roche and is a consultant for Merz.

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Authors and Affiliations

  1. Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA

    Eric J. Nunes, Patrick A. Randall, Alexavier Estrada, Brian Epling, Evan E. Hart, Christie A. Lee, Mercè Correa & John D. Salamone

  2. Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie, Universität Bonn, Bonn, Germany

    Younis Baqi & Christa E. Müller

  3. Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071, Castelló, Spain

    Mercè Correa

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  1. Eric J. Nunes
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Correspondence to John D. Salamone.

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Nunes, E.J., Randall, P.A., Estrada, A. et al. Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology 231, 727–736 (2014). https://doi.org/10.1007/s00213-013-3285-4

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