Serotonin neurons in the dorsal raphe control food-craving-like behavior during pregnancy in mice

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.