Impact of Adolescent Nicotine Exposure in Pre- and Post-natal Oxycodone Exposed Offspring.

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.