Journal
PSYCHOPHARMACOLOGY
Volume 233, Issue 19-20, Pages 3575-3586Publisher
SPRINGER
DOI: 10.1007/s00213-016-4392-9
Keywords
Accumbens; Motivation; Fatigue; Depression; Anergia; Dopamine
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Funding
- UCONN Research Foundation
- Fundacio Bancaixa/U. Jaume I. [P1.1B2010-43]
- UCONN Psychology department grant
- UCONN SURF grant
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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 mu g/kg IP) shifted choice behavior, significantly decreasing lever pressing and increasing chow intake. Further experiments showed that the adenosine A(2A) 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 mu g/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.
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