PERINATAL EFFECTS OF THC ADMINISTRATION ON THE DEVELOPMENT OF SLEEP AND BREATHING

Perinatal exposure to cannabis has been linked to adverse neurodevelopmental outcomes, yet its impact on the maturation of sleep and respiratory control remains poorly defined. Δ⁹-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, readily crosses the placenta and is transferred through breast milk, exposing the developing brain to exogenous cannabinoids during critical windows of network formation. Here, we examined the effects of continuous perinatal THC exposure on maternal care, the development of postnatal sleep architecture and respiratory control. Pregnant dams received THC (1 mg/kg/day) via subcutaneous osmotic pumps from gestational day 5 to postnatal day (P)14. Maternal care behaviours, including licking, grooming, nursing, and pup retrieval, were recorded from P1 to P14. Offspring underwent longitudinal assessment of sleep–wake organization using nuchal EMG, overt behaviour and EEG activity. Breathing patterns and chemoreflex responses were assessed using head-out and whole body plethysmography under normoxia, hypoxia, and hypercapnia.
Our results show that maternal nursing and grooming were preserved, although THC-treated dams exhibited delayed pup retrieval. In pups, THC exposure accelerated sleep-wake maturation: the normal decline in active sleep and rise in wakefulness seen in controls at P10–11 emerged prematurely at P6. Chemoreflex testing showed that newborn pups displayed an attenuated hypoxic ventilatory responses from P0–P3, due to a smaller decrease in oxygen consumption during hypoxic challenge. Collectively, these findings demonstrate that perinatal THC exposure induces premature maturation of sleep architecture and alters early life respiratory control, underscoring a direct developmental vulnerability of sleep–breathing coordination to early-life cannabinoid exposure.