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Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Treadway MT et al. Trends Cogn Sci. (2019)


Senior Member
Interesting review of research on the impact of inflammation on the dopamine system as well as a theoretical model and computational method trying to connect it all.

Could be a hypothesis as to why Abilify and dopaminergic agents have some partial efficacy in ME, even if it is temporary (so only a part of the ME symptom story, not for example what are the cause(s) of the chronic inflammation).

Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive
Treadway MT et al. Trends Cogn Sci. (2019)
Inflammatory cytokines have been shown to have a direct effect on mesolimbic dopamine (DA) that is associated with a reduced willingness to expend effort for reward. To date, however, the broader implications of this communication between inflammation and mesolimbic DA have yet to be explored. Here, we suggest that the metabolic demands of chronic low-grade inflammation induce a reduction of striatal DA that in turn leads to a steeper effort-discounting curve because of reduced perceived ability (can’t) versus preference (won’t) for reward. This theoretical framework can inform how the mesolimbic DA system responds to increased immunometabolic demands during chronic inflammation, ultimately contributing to motivational impairments in psychiatric and other medical disorders.

News summary from ScienceDaily:

How chronic inflammation may drive down dopamine and motivation
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Psalm 46:1-3
Great Lakes
Here was another similar study

The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

It's very wordy so I have only read portions of it but it says, "Pro-inflammatory cytokines can alter the metabolism of serotonin (5-HT) and dopamine (Felger and Miller, 2012),* effecting dysregulation of associated neurotransmitters, including glutamate, norepinephrine (NE, noradrenalin), and corticosteroids. 5-HT and NE are the major neurotransmitters involved in descending nociceptive modulation..."


Senior Member
I'll wait for it to be verified by other researchers, but I certainly feel that something is hampering my motivation. :sleep: