029 - Evaluating neurobehavioral effects of prenatal opioid exposure in preweanling and adolescent rats
Monday, April 28, 2025
7:00am – 9:15am HST
Publication Number: 29.5056
Shirelle X. Liu, University of Minnesota, Minneapolis, MN, United States; Zia Maxim, University of Minnesota Medical School, Minneapolis, MN, United States; Erin E. Zielinski, University of Minnesota Medical School, Minneapolis, MN, United States; Cresta W. Jones, University of Minnesota Medical School, Minneapolis, MN, United States; Peter Muelken, Hennepin County Medical Center, BURNSVILLE, MN, United States; Sam Howard, Hennepin County Medical Center, Saint Paul, MN, United States; Sarah Wilde, Hennepin Healthcare Research Institute, Minneapolis, MN, United States; Paul E. Thalmann, University of Minnesota Twin Cities, Minneapolis, MN, United States; Phu V. Tran, University of Minnesota Medical School, Minneapolis, MN, United States; Andrew Harris, Hennepin Healthcare Research Institute, Minneapolis, MN, United States
Graduate student University of Minnesota Minneapolis, Minnesota, United States
Background: The opioid epidemic has significantly increased the number of infants admitted to neonatal intensive care units for neonatal opioid withdrawal syndrome. However, the long-term behavioral and cognitive deficits associated with prenatal opioid exposure in youth remain to be fully characterized, limiting the development of more effective preventions and treatments. Objective: To assess the neurodevelopmental risks of prenatal opioid exposure in preweanling and adolescent rats. Design/Methods: Pregnant rats received daily subcutaneous injections of morphine sulfate (4-8 mg/kg/week, with increments of 2 mg/kg/week) from gestational day (G) 1 to postnatal day (PND) 0. Control animals received daily injections of an equivalent volume of saline. We then evaluated the neurobehavioral outcomes of prenatal morphine exposureincluding cognition, sociability, and opioid addiction vulnerabilityin preweanling and adolescent rats on locomotor activity (PND 19-21), novel object recognition (PND 21), social approach and recognition (PND 26), and morphine self-administration (MSA, morphine 0.4 mg/kg/infusion, beginning PND 40). A separate group of pregnant rats received morphine injections at a higher dose (high-dose group, morphine 8-16 mg/kg/week, with increments of 4 mg/kg/week) from G 1 to PND 0. Offspring from the high-dose group were tested for MSA beginning at PND 40. Data were analyzed using independent sample t-tests or ANOVA followed by Sidak's multiple comparison tests. Significance was set at p < 0.05. Results: Compared to the saline control group (n = 25), prenatal morphine-exposed rats in the low-dose group (n = 16) exhibited hyperactivity during the preweanling period in the first of three locomotor tests (p = 0.01). Prenatal morphine-exposed rats also failed to distinguish between novel and familiar objects on PND 21 (p < 0.05), and showed reduced social approach during adolescence (p < 0.01). Groups did not differ in terms of social recognition, where both groups similarly recognized familiar versus unfamiliar rats, nor in active lever pressing during the acquisition period of MSA beginning in late adolescence. In contrast, offspring from the high-dose group (n = 11) exhibited higher active lever pressing during the acquisition period compared to saline controls (p < 0.01).
Conclusion(s): These data suggest that prenatal opioid exposure may lead to attention deficit hyperactivity disorder, cognitive deficits, social deficits, and increased addiction vulnerability in childhood and adolescence, supporting the utility of this model for evaluating effects of prenatal opioid exposure.
