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Impact of Adolescent Nicotine Exposure in Pre- and Post-natal Oxycodone Exposed Offspring
Adrian Flores1, Austin Gowen1, Victoria L Schaal1
1Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Insights
Perinatal opioid exposure increases adolescent vulnerability to nicotine. Offspring exposed to oxycodone in utero (IUO) or postnatally (PNO) showed neurochemical and behavioral changes during nicotine withdrawal.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Perinatal opioid exposure, particularly oxycodone, is linked to neurodevelopmental deficits in offspring.
- The interaction between prenatal/postnatal opioid exposure and adolescent nicotine use remains understudied.
- Nicotine exposure during adolescence is a significant public health concern.
Purpose of the Study:
- To investigate the effects of escalating adolescent nicotine exposure and withdrawal on offspring with in utero (IUO) and postnatal (PNO) oxycodone exposure.
- To characterize neurobiological and behavioral alterations resulting from combined exposures.
- To identify vulnerabilities associated with nicotine use in early adolescence following perinatal opioid exposure.
Main Methods:
- Utilized an integrated systems approach combining Western blot, RT-qPCR, and behavioral assays.
- Examined synaptic protein expression, central nervous system immune markers, and peripheral nicotine metabolism.
- Assessed nociception and anxiety-like behaviors in adolescent offspring under escalating nicotine exposure and withdrawal conditions.
Main Results:
- Synaptic protein alterations, including synaptophysin upregulation, were observed in IUO-withdrawal animals.
- RT-qPCR confirmed immune dysfunction within the central nervous system.
- Increased peripheral nicotine catabolism was noted in IUO offspring, alongside subtle deficits in nociception and anxiety-like behaviors during withdrawal.
Conclusions:
- This study provides the first evidence of heightened vulnerabilities in PNO- and IUO-exposed offspring to adolescent nicotine exposure and withdrawal.
- Combined perinatal opioid and adolescent nicotine exposure significantly impacts neurobiological pathways and behavior.
- Findings highlight the critical need to address polysubstance use in vulnerable adolescent populations.
Abstract:
Perinatal exposure to prescription opioids pose a critical public health risk. Notably, research has found significant neurodevelopmental and behavioral deficits between in utero (IUO) and postnatal (PNO) oxycodone-exposed offspring but there is a notable gap in knowledge regarding the interaction of these groups to other drug exposure, particularly nicotine exposure. Nicotine's widespread use represents a ubiquitous clinical interaction that current research does not address. Children often experiment with drugs and risky behavior; therefore, adolescence is a key timepoint to characterize. This study employed an integrated systems approach to investigate escalating nicotine exposure in adolescence and subsequent nicotine withdrawal in the IUO- and PNO-offspring. Western blot analysis found synaptic protein alterations, especially upregulation of synaptophysin in IUO-withdrawal animals. RT-qPCR further validated immune dysfunction in the central nervous system (CNS). Peripheral nicotine metabolism was consistent with increased catabolism of nicotine concerning IUO animals. Lastly, behavioral assays found subtle deficits to withdrawal in nociception and anxiety-like behavior. This study showed, for the first time, the vulnerabilities of PNO- and IUO-exposed groups concerning nicotine use during early adolescence and withdrawal. Graphical Abstract.
