Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.
Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.
The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.
“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.
The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
Newly identified brain circuit plays a key role in satiety response
The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.
Importantly, the results also provide clues about how methylphenidate can lead to weight loss.
Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.
He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”
The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.
“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
Brain signals that control portion size
Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.
The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.
They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.
There were four main findings:
- DA-VTA neurons were activated immediately before the cessation of each feeding bout.
- Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
- Activating DRD1-LPBN neurons inhibited feeding.
- Mice that lacked the DRD1 gene ate much more and gained weight.
“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.
The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.