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Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure

Katherine E Odegaard1, Victoria L Schaal1, Alexander R Clark1

  • 1Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

Translational Psychiatry
|September 24, 2020
PubMed

Insights

Opioid exposure during and after pregnancy, including oxycodone, harms offspring neurodevelopment and behavior across generations. This preclinical study reveals lasting anxiety and social deficits, highlighting risks for future generations.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • Opioid abuse during and after pregnancy is a growing public health issue.
  • Previous research indicates prenatal opioid exposure impairs offspring neurodevelopment.
  • Limited understanding exists regarding comparative developmental effects of in utero versus postnatal opioid exposure and hereditary influences.

Purpose of the Study:

  • To investigate the comparative neurodevelopmental and behavioral effects of oxycodone exposure in utero (IUO) and postnatally (PNO) in a rat model.
  • To examine the intergenerational impact of such exposures.
  • To identify underlying molecular mechanisms, including gene expression changes.

Main Methods:

  • Utilized a preclinical rat model for oxycodone exposure during gestation and lactation.
  • Conducted RNA sequencing to analyze gene expression alterations in exposed offspring across two generations.
  • Performed behavioral studies to assess neurodevelopmental and behavioral outcomes, including anxiety and social deficits.
  • Validated gene expression changes using RT-PCR.

Main Results:

  • Observed significant phenotypic changes in offspring exposed to oxycodone IUO and PNO, across both the first and second generations.
  • RNA sequencing revealed significant alterations in the expression of key synaptic genes in exposed offspring.
  • Identified differential expression of neuropeptides within the hypocretin system, implicated in addiction.
  • Behavioral assessments showed persistent anxiety-like behaviors and social deficits in exposed offspring, extending to subsequent generations.

Conclusions:

  • Oxycodone exposure during and after pregnancy disrupts neurodevelopment in offspring.
  • These disruptions manifest as lasting behavioral deficits, including anxiety and social impairments.
  • The effects are intergenerational, impacting subsequent generations.
  • This study identifies the hypocretin system as a potential molecular target for understanding opioid-induced neurodevelopmental and behavioral changes.

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