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-1Ī²) 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-1Ī² (1.0ā4.0 Ī¼g/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 MSX-3 to reverse the behavioral effects of IL-1Ī². MSX-3 attenuated the effort-related impairments produced by IL-1Ī², increasing lever pressing and also decreasing chow intake. In the same dose range that shifted effort-related choice behavior, IL-1Ī² 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-1Ī² did not affect core body temperature.
Conclusions
These results indicate that IL-1Ī² 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.