Chronic hyperprolactinemia is associated with enhanced high-fat diet binge eating in female mice

Prolactin is fundamental for pregnancy and lactation, and also has numerous metabolic roles including the stimulation of appetite. Mice with chronic hyperprolactinemia display increased food intake, enhanced expression of orexigenic genes in hypothalamic brain centers, and also develop obesity. Here, we tested whether the consumption of a rewarding high-fat diet (HFD) is altered in a mouse model of chronic hyperprolactinemia: LacDrd2KO mice, which lack dopamine Drd2 receptors in lactotrophs, preventing dopamine inhibition of prolactin secretion. We exposed control and LacDrd2KO mice to a binge-like eating protocol in which satiated mice have access to a HFD pellet for 2-h on four consecutive days. We found that both control and LacDrd2KO animals displayed binge-like eating of HFD, and that hyperprolactinemic mice nearly doubled their HFD intake compared to controls. Subsequently, we analyzed the activation of mesocorticolimbic brain nuclei involved in reward processing. We observed that, in response to HFD consumption, c-Fos levels were higher in dopaminergic neurons of the parabrachial pigmented area within the ventral tegmental area (VTA), a key brain center involved in reward regulation, and also in the core subdivision of the nucleus accumbens (Acb), the main target of dopaminergic VTA neurons. Furthermore, hyperprolactinemic mice had greater c-Fos activation in dopaminergic neurons of the VTA in response to HFD consumption, compared to control animals. Finally, c-Fos levels in the hypothalamic arcuate nucleus, mainly involved in the control of homeostatic food intake, were lower in LacDrd2KO mice and unaffected by HFD exposure. Current results suggest that chronic hyperprolactinemia is associated with increased consumption of a rewarding stimulus, engaging the activation of dopaminergic neurons in the VTA.