Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization

• DOI: 10.1007/s00213-016-4392-9
• Publication Date: 2016-08-06T20:56:54Z
• Authors: Samantha E. Yohn; Yumna Arif; Allison Haley; Guiseppe Tripodi; Younis Baqi; Christa E. Müller; Noemi San Miguel; Mercè Correa; John D. Salamone
• Keywords: Neurochemical; Anhedonia; Microdialysis; Stimulant; Conditioned place preference

Motivational dysfunctions such as anergia, fatigue, and reduced effort expenditure are common in patients with depression and other disorders. Pro-inflammatory cytokines are implicated in depression, and cytokine administration induces motivational deficits in humans.These studies focused on the effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.Rats were assessed using the concurrent fixed ratio 5-lever pressing/chow feeding choice procedure, which measures the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a concurrently available but less preferred substitute (lab chow).IL-6 (2.0-8.0 μg/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing chow intake. Further experiments showed that the adenosine A2A antagonist MSX-3 and the stimulant methylphenidate attenuated the effort-related impairments produced by IL-6, increasing lever pressing and decreasing chow intake in IL-6 treated rats. The same doses of IL-6 did not alter food intake or preference in parallel free-feeding choice studies, demonstrating that these low doses were not altering preference for the high carbohydrate pellets or generally suppressing appetite. Also, IL-6 did not affect body temperature. Microdialysis studies showed that 8.0 μg/kg IL-6 significantly decreased extracellular dopamine in nucleus accumbens core.In summary, IL-6 reduces the tendency to work for food, even at low doses that do not produce fever or loss of appetite. Dopaminergic mechanisms may be involved in these effort-related effects. This research has implications for the involvement of cytokines in motivational dysfunctions such as anergia and fatigue.