Summary:
Researchers have identified a specific neural circuit and molecular mechanism that explain the strong food cravings many people experience during pregnancy. The study shows that pregnancy increases activity of the SK3 potassium channel in serotonin-producing neurons of the dorsal raphe nucleus (DRN), suppressing their firing and shifting reward signaling in a way that promotes stronger motivation for calorie-dense, palatable foods.
Key Facts:
- Reduced Serotonin Neuron Activity: During pregnancy, serotonin neurons in the dorsal raphe nucleus show a lower baseline firing rate, which in animal models directly corresponds with heightened food-seeking and craving-like behaviors.
- SK3 Potassium Channel Involvement: Pregnancy upregulates the small-conductance calcium-activated potassium channel SK3 in DRN serotonin neurons. Removing SK3 specifically from these neurons preserved their normal firing during gestation and markedly reduced cravings.
- Reward Circuit Interaction: The team mapped a functional inhibitory projection from DRN serotonin neurons to the ventral tegmental area (VTA), a central node of the brain’s dopamine-driven reward system. Manipulating this pathway altered pregnancy-associated food cravings.
Source: LSU Pennington Biomedical Research Center
Decoding the Neurobiology of Maternal Food Cravings
Many people describe intense cravings for sweet, salty, or high-calorie foods during pregnancy. While cultural explanations often frame these cravings as a quirk of gestation, they can have real health consequences: excessive intake during pregnancy increases risks for gestational diabetes, excess maternal weight gain, and long-term metabolic problems for both parent and child.
Until recently, the neural mechanisms driving this motivational shift were not well understood. A collaborative team of researchers led by Dr. Yanlin He (Pennington Biomedical Research Center), Dr. Pingwen Xu (University of Illinois Chicago), and Dr. Chunmei Wang (Baylor College of Medicine) published a study in Nature Neuroscience that identifies both the cellular mechanism and the circuit-level changes that promote food cravings during pregnancy.
The Dorsal Raphe and the SK3 Ion Channel
The researchers focused on the dorsal raphe nucleus, a brainstem region rich in serotonin-producing (5-HT) neurons that influence mood, appetite, and satiety. Electrophysiological recordings revealed a clear reduction in the spontaneous firing rate of DRN serotonin neurons during pregnancy. This decreased activity coincided with increased consumption of palatable foods in pregnant mice.
Investigating the cellular basis for this reduced firing, the team identified enhanced activity of the SK3 potassium channel (small-conductance calcium-activated potassium channel 3) in DRN serotonin neurons during pregnancy. SK3 channels help hyperpolarize neurons by allowing potassium to leave the cell, effectively acting as a brake on electrical excitability. When SK3 activity rises, serotonin neurons fire less frequently.
To test causality, researchers used genetic tools to remove SK3 selectively from DRN serotonin neurons in female mice. Those animals maintained normal serotonergic firing through pregnancy and showed substantially reduced food-craving-like behavior. Conversely, overexpressing SK3 in nonpregnant females reproduced both the neurophysiological suppression of serotonin firing and the elevated craving behaviors seen during pregnancy.
Connecting Serotonin to the Brain’s Reward System
The next question was how reduced DRN serotonin firing leads to stronger motivation for palatable food. Anatomical and functional tracing revealed an inhibitory projection from DRN serotonin neurons to the ventral tegmental area (VTA), a key component of the mesolimbic dopamine reward pathway. Under typical conditions, robust serotonin signaling from the DRN provides inhibitory control over reward-driven seeking.
When pregnancy increases SK3 activity and suppresses serotonin firing, that inhibitory influence on the VTA weakens. The resulting disinhibition allows the VTA reward circuitry to amplify motivation and drive consumption of highly palatable foods. In experimental manipulations, activating the DRN-to-VTA pathway reduced craving-like behavior in pregnant mice, while silencing the pathway in nonpregnant mice generated similar craving responses.
Clinical Perspective and Future Directions
These findings clarify a biological pathway that could underlie why some people experience strong food cravings and excessive weight gain during pregnancy. At the same time, the authors emphasize caution: these results derive from animal studies, and directly manipulating serotonin signaling in pregnant people could carry risks.
Dr. He noted that further research is needed to understand how pregnancy hormones such as progesterone and estrogen interact with SK3 channels and DRN neurons. Future translational work will aim to identify safe, targeted strategies to prevent excessive gestational weight gain and reduce the risk of maternal metabolic disease without harming fetal development.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context provided by editorial staff.
About this Genetics and Neurology Research:
- Media Contact: Ernie Ballard
- Source: Pennington Biomedical Research Center
- Image Credit: Image generated for Neuroscience News
- Original Research is Closed Access: Nature Neuroscience (September 18, 2026). Title: “Serotonin neurons in the dorsal raphe control food-craving-like behavior during pregnancy in mice.” Authors: Jane R. Abolafia, Hanna Hameedy, Lakshmi Prakash, Ziqi Wang, Elze Amileviciute, Srikar Dudipala, and Alexander Jaworski.
- DOI: 10.1038/s41593-026-02445-3
Abstract
Serotonin neurons in the dorsal raphe control food-craving-like behavior during pregnancy in mice
Pregnancy triggers physiological changes that can alter feeding behavior, but the specific neural mechanisms were unclear. In this study, pregnant female mice exhibited increased food-craving-like behavior that mirrors many patterns reported in humans.
The authors demonstrate that firing activity of DRN serotonin (5-HTDRN) neurons is reduced during pregnancy due to increased SK3 channel activity. Genetic deletion of SK3 from 5-HTDRN neurons prevents the pregnancy-associated reduction in firing and decreases craving-like behavior in pregnant mice. Conversely, overexpressing SK3 in 5-HTDRN neurons of virgin females reproduces pregnancy-like reductions in firing and increased cravings. Activation of 5-HTDRN projections to the ventral tegmental area inhibits craving-like behavior in pregnant mice.
These results provide new insight into how serotonin signaling modulates food cravings during pregnancy and identify SK3 and the DRN-to-VTA circuit as potential targets for interventions aimed at managing pregnancy-associated appetite changes and reducing maternal obesity risk.