Choline supplementation partially reverses prefrontal neurochemical deficits induced by perinatal opioid exposure

Perinatal opioid exposure often compromises offspring executive function, affects offspring neuroimmune outcomes, and can impair neonatal striatal acetylcholine transmission. Therefore, we sought to examine the impact on prefrontal cortical (PFC) neurotransmission and determine whether adolescent dietary choline supplementation attenuates the effects of perinatal opioid exposure in male offspring. Using a mouse model, we found that perinatal morphine exposure reduced acetylcholine (33%) and choline (49%) in the PFC of male offspring in early adulthood, while leaving the striatum largely unaffected. Adolescent choline supplementation partially restored cholinergic deficits. While morphine exposure did not induce executive function deficits, choline supplementation improved attentional accuracy in the 5-choice serial reaction time task and reduced breakpoint in progressive ratio testing. Choline supplementation did not prevent increases in thigmotaxis after morphine exposure in male offspring. Perinatal morphine exposure increased expression of neuroinflammatory genes Apoe and Cd68 in the male basolateral amygdala, effects that were attenuated by choline supplementation. Together, these findings reveal defined neurochemical and molecular vulnerabilities to perinatal opioid exposure that may be mitigated by dietary choline supplementation. Choline supplementation was beneficial for executive function but did not specifically target morphine-induced behavioral changes. Importantly, this work is relevant for males and future work will assess female offspring.