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

Autor: Minakova E; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA., Mikati MO; Department of Psychiatry, Washington University School of Medicine, Campus Box 8232, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA.; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.; Washington University Pain Management Center, Washington University School of Medicine, St. Louis, MO, USA.; Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis, St. Louis, MO, USA., Madasu MK; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.; Washington University Pain Management Center, Washington University School of Medicine, St. Louis, MO, USA.; Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis, St. Louis, MO, USA., Conway SM; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.; Washington University Pain Management Center, Washington University School of Medicine, St. Louis, MO, USA.; Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis, St. Louis, MO, USA., Baldwin JW; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.; Department of Biology, Washington University School of Medicine, St. Louis, MO, USA., Swift RG; Department of Psychiatry, Washington University School of Medicine, Campus Box 8232, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA., McCullough KB; Department of Psychiatry, Washington University School of Medicine, Campus Box 8232, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA., Dougherty JD; Department of Psychiatry, Washington University School of Medicine, Campus Box 8232, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.; Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA., Maloney SE; Department of Psychiatry, Washington University School of Medicine, Campus Box 8232, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA. maloneys@wustl.edu.; Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA. maloneys@wustl.edu., Al-Hasani R; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA. al-hasanir@wustl.edu.; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA. al-hasanir@wustl.edu.; Washington University Pain Management Center, Washington University School of Medicine, St. Louis, MO, USA. al-hasanir@wustl.edu.; Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis, St. Louis, MO, USA. al-hasanir@wustl.edu.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2022 Dec; Vol. 239 (12), pp. 3859-3873. Date of Electronic Publication: 2022 Oct 21.
DOI: 10.1007/s00213-022-06257-8
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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