ORF51-07 - Mesolimbic Dopamine Signaling Mediates Increased Hedonic Feeding and Food Seeking in Lactating Mice

Lactation represents a critical physiological period that imposes significant energetic demands on mothers and impacts both maternal and offspring health. To meet the demands of milk production and heat generation for their young, lactating mammals drastically increase food intake, consuming 200-300% more food than non-lactating animals. However, the underlying behavioral, molecular, and neural circuit mechanisms driving increased feeding behavior during lactation remain poorly understood.

In this study, we investigated changes in feeding behavior and motivation in lactating mice using automated home cage feeding devices (Feeding Experimentation Devices; FED3). Our results show that lactation alters meal patterns and increases food-seeking behavior. We also observed an increased preference for palatable foods in lactating mice. Given the known role of dopaminergic pathways in regulating food-seeking and hedonic eating, we employed pharmacological, chemogenetic, and imaging techniques to explore changes in these pathways during lactation.

Pharmacological inhibition of dopamine receptors potently reduced meal size and food-seeking behavior in lactating mice, normalizing these behaviors to the levels observed in non-lactating animals. Dopamine receptor antagonism also suppressed the intake of palatable foods during lactation. To investigate functional changes in dopamine signaling, we used in vivo fiber photometry that showed increased responsivity of the Ventral Tegmental Area (VTA) dopamine neurons in lactating mice in response to food. This was accompanied by elevated dopamine release in the nucleus accumbens in lactating animals during feeding tasks. Quantification of the initial dopamine release was correlated to the amount of time spent eating in the entire recording session. This elevated dopamine signaling was ultimately required for promoting both food seeking and palatable food intake during lactation as chemogenetic inhibition of VTA dopamine neurons reduced food seeking and palatable food intake in lactating mice to non-lactating levels. Further, selective inhibition of dopamine receptors using bilateral cannula implanted into the nucleus accumbens produces similar results. Together, these findings provide a circuit basis mediating elevated food seeking and palatable food intake during lactation, providing novel insights into the regulation of maternal energy balance and feeding behavior.