Brain Pathway Links Cancer Inflammation to Loss of Motivation
A new study links inflammation in cancer to dopamine loss, suggesting apathy is biologically driven.
Complete the form below to unlock access to ALL audio articles.
Fatigue and loss of motivation in patients with advanced cancer have long been seen as inevitable side effects of physical decline and weight loss. However, new research from Washington University School of Medicine in St. Louis has identified a specific brain pathway that directly links cancer-related inflammation to a drop in motivation.
Published April 11 in Science, the study examined a mouse model of cachexia, a syndrome often associated with cancer that causes muscle wasting and extreme weight loss. The researchers found that inflammation activates a structure in the brainstem, which in turn suppresses dopamine release in a brain region essential for motivation.
Cachexia
A syndrome often seen in advanced cancer, characterized by severe weight loss, muscle wasting and fatigue, which cannot be reversed by normal nutritional support.
This newly identified pathway suggests that apathy is not merely a byproduct of physical deterioration but is instead the result of distinct biological signaling triggered by inflammation.
Targeting inflammation restored motivation in mice
The research team focused on behavioral symptoms that accompany cachexia but have received limited attention. Using a well-validated model, they mapped brain activity in mice with the condition and pinpointed a set of neurons in the brainstem that responded to the inflammatory molecule interleukin-6 (IL-6).
Interleukin-6 (IL-6)
A cytokine, or signaling molecule, that helps regulate immune responses. Elevated IL-6 levels are associated with inflammation in conditions such as cancer and autoimmune diseases.
These neurons transmitted a signal that reduced dopamine in the nucleus accumbens, a brain region central to reward and motivation. The loss of dopamine made the mice less willing to engage in effortful tasks.
Nucleus accumbens
A region in the brain involved in the reward circuit. It processes dopamine signals and plays a key role in reinforcement and motivation.
To determine if the pathway could be interrupted, the team tested two interventions: boosting dopamine levels and blocking the inflammation-sensing neurons. Both restored the animals’ motivation without affecting tumor growth or weight loss.
Treatment with an antibody targeting IL-6, similar to one approved for rheumatoid arthritis, also reversed apathy in the mice.
Brain circuit implicated in chronic disease-related apathy
IL-6 is elevated in many chronic illnesses, not only cancer. Since the brain structures identified are crucial for motivational processes, the researchers propose that this same inflammatory pathway may underlie apathy in other long-term conditions.
While transient reductions in motivation might be beneficial during acute infections by conserving energy, prolonged apathy can worsen outcomes in chronic diseases. The study’s findings suggest that psychological symptoms such as fatigue and social withdrawal might be treated independently of the disease process that causes them.
By decoupling apathy from physical decline, the study opens new avenues for improving quality of life in patients with advanced illnesses.
Reference: Zhu XA, Starosta S, Ferrer M, et al. A neuroimmune circuit mediates cancer cachexia-associated apathy. Science. 2025;388(6743):eadm8857. doi: 10.1126/science.adm8857
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.
This content includes text that has been generated with the assistance of AI. Technology Networks' AI policy can be found here.
