bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 21, 2025

The use of fentanyl and other opioids during pregnancy is a pressing public health issue due to its association with Neonatal Opioid Withdrawal Syndrome (NOWS) long-term neurobehavioral deficits. Human epidemiologic studies are confounded by both genetic environmental factors that differ between exposed unexposed children. We developed novel rat model perinatal exposure characterize NOWS symptoms investigate enduring behavioral molecular outcomes. Offspring born fentanyl-exposed dams exhibited reduced survival, lower body weight, spontaneous withdrawal symptoms, mechanical hypersensitivity. In adolescence, these rats displayed negative affect, while in adulthood, they showed increased self-administration, heightened drug-seeking reinstatement, elevated corticosterone levels withdrawal. To explore the underpinnings physiological outcomes, we conducted RNA-seq central amygdala adult rats, revealing dysregulated pathways related GPCR signaling, adaptive immune response neurodevelopmental processes. These transcriptional changes provide insights into mechanisms driving addiction vulnerability stress-related behaviors following early exposure. Our findings highlight lasting impact opioid an experimental system avoids many confounds plague humans, underscoring need for preclinical models study consequences. This offers translational relevance developing therapeutic strategies mitigate reduce neuropsychiatric risks associated prenatal

Language: Английский