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

• Published in: Psychopharmacology 2014-02, Vol.231 (4), p.727-736
• Main Authors: Nunes, Eric J., Randall, Patrick A., Estrada, Alexavier, Epling, Brian, Hart, Evan E., Lee, Christie A., Baqi, Younis, Müller, Christa E., Correa, Mercè, Salamone, John D.
• Format: Article
• Language: English
• Subjects: Adenosine A2 Receptor Antagonists - pharmacology; Analysis; Animal behavior; Animals; Biomedical and Life Sciences; Biomedicine; Body Temperature; Choice Behavior - drug effects; Conditioning, Operant - drug effects; Cytokines; Eating - drug effects; Fatigue; Feeding Behavior - drug effects; Food Preferences - drug effects; Interleukin-1beta - administration & dosage; Interleukins; Male; Mental depression; Motivation; Motivation - drug effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological psychology; Psychiatry; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A - metabolism; Recombinant Proteins - administration & dosage; Rodents; Xanthines - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3285-4

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 A 2A 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.