Researchers Highlight Role of GABA and Dopamine in Meal Initiation - Video

A new study published in the journal Metabolism reveals brain circuits and chemical messengers that contribute to the regulation of meal initiation and food intake. The findings have implications for the development of improved therapies to manage obesity, a worldwide epidemic.

“It’s well known that serotonin, a neurotransmitter in the brain, can suppress food intake. This finding led to the development of drugs that interact with serotonin or its receptors to regulate food consumption and obesity,” said corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and associate director of basic sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor. “However, some of these drugs have unwanted side effects, and they are no longer offered to patients. There is a need to better understand how the brain regulates food intake to improve drug design.”

In this study, researchers focused on a little-known component of the serotonin regulation of food intake. They looked for brain circuits and neurotransmitters that regulate the activity of serotonin-producing neurons, activating or inhibiting them at the appropriate periods to reach balanced food consumption

Serotonin is primarily synthesized by neurons in the dorsal Raphe nucleus (DRN) in the midbrain. Serotonin neurons in the DRN project to numerous brain regions, including the arcuate of the hypothalamus (ARH). The team showed that the ARH circuit and two neurotransmitters, GABA and dopamine, play a key role in meal initiation.

“Working with animal models, we found that when the animals are hungry, serotonin-producing neurons in the DRN are inhibited by GABA and dopamine. This reduces the levels of serotonin in the brain, which allows the initiation of a meal,” Xu explained. “As the animals feed and reach satiety, the inhibitory signals on serotonin neurons are reduced and more serotonin is produced to inhibit feeding via projections to the ARH.”

“What's unique about this is that GABA and dopamine act synergistically – when both are present, serotonin neurons appear to be more inhibited than when only one of the neurotransmitters is present,” Xu said.

Reference: Serotonin neurons integrate GABA and dopamine inputs to regulate meal initiation, Conde, Kristine M. et al., Metabolism - Clinical and Experimental, Volume 163, 156099