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Updated: May 9, 2026

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes
Published on: June 28, 2024
Choline supplementation partially reverses prefrontal neurochemical deficits induced by perinatal opioid exposure
Chen Sirois1, Anna G Makela2, Elena V Romanova3,4
1Neuroscience Program, University of Illinois Urbana Champaign, 405 North Mathews Avenue, Urbana, IL, 61801, USA.
Insights
Perinatal opioid exposure impacts male offspring brain function. Adolescent choline supplementation partially restored neurotransmitters and improved some executive functions, but did not reverse all effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Perinatal opioid exposure can negatively affect offspring neurodevelopment, including executive function and neuroimmune responses.
- Opioid-induced deficits in acetylcholine transmission have been observed in the striatum, but prefrontal cortex (PFC) effects are less understood.
Purpose of the Study:
- To investigate the impact of perinatal morphine exposure on prefrontal cortical (PFC) neurotransmission in male offspring.
- To determine if adolescent dietary choline supplementation can mitigate the neurochemical and behavioral effects of perinatal opioid exposure.
Main Methods:
- A mouse model was used to study perinatal morphine exposure and adolescent choline supplementation.
- Neurotransmitter levels (acetylcholine, choline) in the PFC and striatum were measured.
- Behavioral tests (5-choice serial reaction time task, progressive ratio testing, thigmotaxis) assessed executive function and anxiety-related behaviors.
- Gene expression of neuroinflammatory markers (Apoe, Cd68) in the basolateral amygdala was analyzed.
Main Results:
- Perinatal morphine exposure significantly reduced acetylcholine and choline levels in the male offspring PFC, with minimal effects on the striatum.
- Adolescent choline supplementation partially restored these cholinergic deficits.
- While morphine did not impair executive function, choline supplementation improved attentional accuracy and reduced motivation in behavioral tasks.
- Choline supplementation attenuated morphine-induced increases in neuroinflammatory gene expression (Apoe, Cd68) in the basolateral amygdala.
- Choline supplementation did not prevent increased thigmotaxis in morphine-exposed offspring.
Conclusions:
- Perinatal opioid exposure induces specific neurochemical deficits in the male offspring PFC and neuroinflammatory changes in the amygdala.
- Adolescent choline supplementation offers partial neurochemical and behavioral benefits, including improved executive function and reduced neuroinflammation.
- Choline supplementation shows promise in mitigating some, but not all, adverse effects of perinatal opioid exposure.
Abstract:
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.
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