Neurodevelopmental Changes in Offspring Prenatally Exposed to Opioids in Human Children and Rodent Models: A Review

Abstract

The number of infants born to opioid-dependent pregnant women in North America is a growing problem. Studies that focus on the long-term effects of neurodevelopmental changes of prenatal opioid exposure in human infants are however limited. The use of rodent models to evaluate these changes may provide some insight. This review focuses on studies of rodent models exposed to opioids such as morphine, heroin, oxycodone, buprenorphine, methadone, and l-α-acetylmethadol in uteroand briefly discusses the neural and behavioural effects in human children. Most of the rodent studies reported the following neural effects: increases in caspase-3 and Bax/Bcl-2 ratio, altered NMDA activity, and decreases in BDNF expression in the offspring prenatally exposed to opioids. In addition, they showed decreases in synaptic plasticity, LTP, LTD, dendritic length, and dendritic branch number. The exposed rodent offspring were more inclined to perform poorly in the behavioural tests. Likewise, some of the human studies reported a significant difference between the exposed group and the control; however, other studies reported insignificant or no significant differences after correcting for covariates. Most of the studies suggest an impairment in learning and memory in the rodent offspring and deficits in behaviour and cognition in human children; however, this was not always the case. It is still not clear whether the effects of prenatal opioid exposure are due to the opioid itself being the prime factor, as various factors may also contribute to the results. Further studies of the effects of early opioid exposure on neurodevelopment in the offspring are required.