Impact of Prenatal Methamphetamine Exposure on Dopaminergic Neuroimmune Interactions

Abstract ID 95326 Poster Board 323 Methamphetamine, most commonly used by child-bearing age individuals, is a significant concern for pregnant women in the United States. Methamphetamine use during pregnancy is linked to various developmental issues in children, such as impaired intellectual functioning, memory, language development, and emotional regulation. The molecular mechanisms by which in utero exposure to methamphetamine leads to altered offspring growth and behavior are still largely unknown. The long-term goal of the present study is to investigate how chronic prenatal exposure to methamphetamine affects neuroimmune interactions within the dopaminergic reward pathway, focusing on its potential impact on the maturation of brain regions like the striatum and prefrontal cortex. We hypothesize methamphetamine exposure modulates the maturation of midbrain-originating innervation of the striatum and/or prefrontal cortex by altering neuroimmune interactions. Experimental Design and Methods: After observation of a vaginal plug (embryonic day 0.5), dams were administered 5 mg/kg (s.c.) of methamphetamine daily until parturition. Starting on postnatal day (PND) 4, the following battery of behavioral and developmental tests was conducted through weaning age: maternal behavior observation (PND 6, 14), pup retrieval test (PND 6), surface righting reflex (PND 4-6), negative geotaxis test (PND 6, 8, 10, 14), and open field test (PND 20). After the final day of testing on PND20, dams and pups were perfused, and brains were collected for immunofluorescent analysis. Results and Ongoing Studies: Our preliminary data suggests that chronic exposure to methamphetamine during pregnancy may negatively affect maternal gestational weight gain, litter size, postpartum maternal behavior, and pup performance on the negative geotaxis task. Consistent with the literature, these data show the implications of methamphetamine use during pregnancy on mothers and offspring development. While the second phase of the project analyzing the innervation of dopaminergic terminals in the striatum and prefrontal cortex and their interactions with glia are currently ongoing, we are excited to share our results at ASPET 2024. Ultimately, we hope this work will shed some light on how prenatal methamphetamine exposure affects dopaminergic pathway development and confers increased susceptibility to neurodevelopmental disease.