Dual hypocretin receptor antagonists enhance sleep and nursing behavior in lactating rats

Hypocretins (also known as orexins) are neuropeptides that regulate the sleep-wake cycle and modulate a variety of behaviors, including maternal behavior. They act through two receptor subtypes: hypocretin receptor 1 (HcrtR1) and hypocretin receptor 2 (HcrtR2). Hypocretin signaling is dynamically modulated across reproductive states, including the postpartum period, a stage characterized by increased wakefulness and fragmented sleep, likely reflecting the physiological demands of offspring care. Dual orexin receptor antagonists (DORAs), such as suvorexant, are clinically used as hypnotics, suggesting their potential relevance for restoring sleep during the postpartum period. However, their effects during lactation remain largely unexplored.

To examine the impact of the DORA Suvorexant on sleep and maternal behavior in lactating rats.

Lactating and virgin female rats were implanted with electrodes for polysomnographic recording. Using a counterbalanced within-subject design, Suvorexant was administered orally on separate recording sessions at 0, 10 (SUV10), and 30 mg/kg (SUV30) to virgin rats in diestrus and to lactating rats between postpartum days 4 and 8. Sleep recordings and maternal behaviors were assessed during the light phase for six hours following the administration of the drug.

Suvorexant reduced wakefulness and increased slow wave sleep, intermediate state, and REM sleep in both groups, with a stronger effect in virgin females. In lactating rats, Suvorexant increased nursing time and milk ejections, while reducing active maternal behavior such as pup-licking.

These findings demonstrate that dual hypocretin receptor antagonism produces hypnotic effects and selectively modulates maternal behavior, increasing nursing while reducing active maternal behavior.