Learning and Memory Performance in a Rat Model of Perigestational Opioid Exposure

Abstract

Rationale: Nearly one third of women of reproductive age in the United States are prescribed opioids annually; 14% will fill an opioid prescription during pregnancy, and one in five report misuse. Opioid use during pregnancy has given rise to an increasing population of infants born with gestational opioid exposure. At school age, these children show neurodevelopmental impairment and higher rates of learning disability. Objectives: To characterize how exposure to exogenous opioids during brain development affects learning and memory performance, our lab has developed a rat model of perigestational opioid exposure that closely recapitulates a clinically relevant dosing timeline by beginning morphine exposure before pregnancy and continuing through the first postnatal week. Male and female offspring generated from this model were assessed on several facets of learning and memory during adolescence. Results: Here, we report that morphine exposure selectively impaired spatial learning, as measured by the Barnes Maze, and associative learning, as measured by an Attentional Set Shift Task, without significantly impacting working or short-term memory. Environmental enrichment rescued the spatial learning deficit in males but not females. Conclusion: Our findings suggest that gestational opioid exposure can impair performance in complex cognitive tasks that are attenuated by non-invasive, non-pharmacological intervention.