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.

Scientific Reports
|May 7, 2026
PubMed

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.

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