During pregnancy, physiological changes can alter food intake behaviors. However, the underlying neural mechanisms remain unclear. Here we show that female mice exhibit food-craving-like behavior during pregnancy, mirroring many patterns described in humans.
We show that 5-HTDRN neuronal firing activity is reduced during pregnancy through increased small-conductance calcium-activated potassium type 3 (SK3) ion-channel activity. Genetic knockout of SK3 ion channels from 5-HTDRN neurons abolishes the pregnancy-associated suppression in 5-HTDRN neuronal firing activity and reduces food-craving-like behavior in pregnant mice. Conversely, overexpression of SK3 in 5-HTDRN neurons mimics pregnancy-induced food-craving-like behavior in virgin female mice.
Moreover, activation of 5-HTDRN projections to ventral tegmental area inhibits food-craving-like behavior in pregnant mice. These findings provide novel insights into the role of 5-HT signaling in modulating food cravings during pregnancy and highlight potential targets for managing pregnancy-associated appetite dysregulation and maternal obesity in humans. This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout A reporting summary for this article is available as a Supplementary Information file.
Single-cell RNA-seq data are accessible from the NCBI GEO database (GSE335067). Source data and Supplementary Data are provided with this paper. C., Flammer, A., Slatch, C. & Hormes, J.
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Food craving-like episodes during pregnancy are mediated by accumbal dopaminergic circuits. Metab. 4, 424–434 (2022). Craving more than food: the implications of pica in pregnancy.
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