Research reveals new connection between circadian rhythms, metabolism, and addiction

A new study highlights an existing connection between specific neurons and peripheral organs revealing a link between substance use disorders and metabolic dysfunctions.

The research, published in the journal, Proceedings of the National Academy of Sciences, was conducted by the University of California Irvine. Scientists explored how the disruption of normal neuronal functions affects metabolic activity and may move the body to an altered state away from homeostasis, which could contribute to the drug seeking behaviors exhibited by people with substance use disorders, according to Emiliana Borrelli, PhD, professor of Microbiology & Molecular Genetics at UCI School of Medicine.

By analyzing the liver metabolome of mice deficient in the expression of the dopamine D2 receptor (D2R) in striatal medium spiny neurons, the researchers found profound changes in the liver circadian metabolome compared to control mice. In addition, they found that activation of dopaminergic circuits by acute cocaine administration reprograms the circadian liver metabolome.

“D2R signaling in medium spiny neurons is key for striatal output and is essential for regulating the first response to the cellular and rewarding effects of cocaine,” Borrelli said. “Thus, our results suggest that changes in dopamine signaling in specific striatal neurons evoke major changes in liver physiology. Dysregulation of liver metabolism could contribute to an altered allostatic state and therefore be involved in continued use of drugs.”

The study concluded that dopamine D2 receptors (D2R) in striatal medium spiny neurons (MSNs) play a key role in regulating diurnal liver metabolic activities. In addition, according to Borelli, drugs that increase dopamine levels, such as cocaine, disrupt circadian metabolic profiles in the liver, which is exacerbated by loss of D2R signaling in MSNs.

These results uncover a strict communication between neurons/brain areas and liver metabolism as well as the association between substance use and systemic deficits.