In utero and post-natal opioid exposure followed by mild traumatic brain injury contributes to cortical neuroinflammation, mitochondrial dysfunction, and behavioral deficits in juvenile rats

Developmental outcomes with perinatal exposure (DOPE) to prescription opioids

“…Beyond the cognitive implications, preclinical POE models have shed light on a range of behavioral deficits in offspring, including anxiety-like behaviors, depressive-like indicators, and analgesic deficits [ 93 – 96 ]. Among these, the most extensively studied deficit is anxiety-like behavior, which assessed through various assays such as open field, startle response, elevated plus maze, marble bury assay, and novel environment testing [ 97 – 102 ].…”

“…A search on PubMed and Google Scholar yielded only eight research articles addressing this limitation in perinatal research of analgesics, with just six articles focusing on opioids–none of which studied the impact of oxycodone [ 107 – 114 ]. Separate investigations focused on maternal care, outside of cross-fostering, found no significant difference in pup retrieval, which serves as a proxy for maternal care, between POE dams and control dams [ 96 ]. However, some other researchers found differences in vocalizations between dams, and the translational significance of these differences remains uncertain.…”

“…While recent research by Flores et al has indicated that nicotine and other low-dose stimulants may not cause immediate harm to adolescent-exposed offspring, their vulnerability to other psychoactive substances like alcohol, anesthetics, and future analgesic use remains poorly understood [ 84 ]. These substances have been implicated in recent bioinformatics studies focused on the transcriptional and translational level [ 54 , 78 , 95 , 96 ]. However, comprehensive investigations into the susceptibility of POE offspring to future substance use, using methods such as self-administration or preference testing are lacking.…”

“…Gowen and colleagues have recently also shown that POE offspring are more susceptible to mild traumatic brain injury (mTBI) using a robust rotational brain injury model in conjunction with prenatal opioid exposure [ 96 ]. This study also revealed that mTBI exacerbated injury-related changes in immune profiles and oxidative stress at the mitochondrial level, finding dysfunction in multiple complexes in the electron transport chain.…”