Neurochemical drivers of effort: The roles of dopamine and beyond in physical and cognitive exertion.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical and clinical studies without systematic review methodology or meta-analysis
PubMed 42000098 · doi:10.1016/j.neubiorev.2026.106696
What was done
The authors synthesized evidence from animal and human studies involving behavioral, pharmacological, computational, and neuroimaging paradigms. The review assessed how dopamine interacts with non-dopaminergic systems—including adenosine, GABA, serotonin, norepinephrine, acetylcholine, and metabolic signals—to regulate physical and cognitive effort-based decision-making.
What was found
The abstract reports no quantitative metrics or statistical values. Qualitatively, the review found that while dopamine remains critical for energizing behavior and promoting effort exertion, alterations in non-dopaminergic neuromodulatory pathways can independently bias effort cost-benefit evaluations even when reward sensitivity is preserved.
Why it matters
This multi-system framework helps explain why motivational syndromes such as apathy and anhedonia often persist despite standard dopaminergic pharmacotherapy in conditions like depression and Parkinson's disease. Shifting beyond single-transmitter models provides a mechanistic basis for developing more targeted therapeutic strategies.
Limits
The abstract describes a narrative review without detailing systematic search criteria, quality appraisal of included literature, or total study sample sizes. Findings rely heavily on combining disparate animal models and human experimental paradigms, which may not directly generalize across diverse clinical populations.
Cited by
- supports Physical movement and cognitive effort are governed by the same catecholamine systems, primarily dopamine, with norepinephrine and epinephrine generating focus.