Perinatal oxycodone exposure causes long-term sex-dependent changes in weight trajectory and sensory processing in adult mice

Elena Minakova, Marwa O. Mikati, Manish K. Madasu, Sineadh M. Conway, Justin W. Baldwin, Raylynn G. Swift, Katherine B. McCullough, Joseph D. Dougherty, Susan E. Maloney, Ream Al-Hasani

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: In utero opioid exposure is associated with lower weight and a neonatal opioid withdrawal syndrome (NOWS) at birth, along with longer-term adverse neurodevelopmental outcomes and mood disorders. While NOWS is sometimes treated with continued opioids, clinical studies have not addressed if long-term neurobehavioral outcomes are worsened with continued postnatal exposure to opioids. In addition, pre-clinical studies comparing in utero only opioid exposure to continued post-natal opioid administration for withdrawal mitigation are lacking. Objectives: Here, we sought to understand the impact of continued postnatal opioid exposure on long term behavioral consequences. Methods: We implemented a rodent perinatal opioid exposure model of oxycodone (Oxy) exposure that included Oxy exposure until birth (short Oxy) and continued postnatal opioid exposure (long Oxy) spanning gestation through birth and lactation. Results: Short Oxy exposure was associated with a sex-specific increase in weight gain trajectory in adult male mice. Long Oxy exposure caused an increased weight gain trajectory in adult males and alterations in nociceptive processing in females. Importantly, there was no evidence of long-term social behavioral deficits, anxiety, hyperactivity, or memory deficits following short or long Oxy exposure. Conclusions: Our findings suggest that offspring with prolonged opioid exposure experienced some long-term sequelae compared to pups with opioid cessation at birth. These results highlight the potential long-term consequences of opioid administration as a mitigation strategy for clinical NOWS symptomology and suggest alternatives should be explored.

Original languageEnglish
Pages (from-to)3859-3873
Number of pages15
JournalPsychopharmacology
Volume239
Issue number12
DOIs
StatePublished - Dec 2022

Keywords

  • Neonatal opioid withdrawal syndrome
  • Nociceptive processing
  • Opioid
  • Oxycodone
  • Sex differences

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