Related Experiment Video
Updated: Aug 1, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Perinatal Fentanyl Exposure Leads to Long-Lasting Impairments in Somatosensory Circuit Function and Behavior
Jason B Alipio1, Catherine Haga1, Megan E Fox1
1Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Insights
Prenatal fentanyl exposure causes lasting neurodevelopmental problems in adolescent mice, affecting sensory processing and brain circuitry. These effects stem directly from fentanyl
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- The opioid epidemic poses risks to adolescent neurodevelopment.
- A precise preclinical model is crucial for studying prenatal opioid exposure effects.
- Fentanyl's impact on the developing brain requires thorough investigation.
Purpose of the Study:
- To establish and utilize a novel preclinical model for perinatal fentanyl exposure.
- To investigate the dose-dependent, long-term consequences of prenatal fentanyl on somatosensory function and behavior.
- To elucidate the underlying circuit, network, and molecular alterations in the developing brain.
Main Methods:
- A novel preclinical model of perinatal fentanyl exposure in mice.
- Behavioral assessments, including sensory-related deficits and withdrawal signs.
- In vitro electrophysiology, electrocorticography (ECoGs), morphologic analysis, and mRNA expression profiling.
Main Results:
- Perinatal fentanyl exposure induced dose-dependent somatosensory deficits and withdrawal signs lasting into adolescence.
- Adolescent mice showed impaired sensory adaptation, reduced primary somatosensory (S1) function, and altered synaptic plasticity (reduced excitation in S1, increased excitation in anterior cingulate cortex).
- Morphological changes included reduced dendritic complexity and altered cortical gene expression.
Conclusions:
- Prenatal fentanyl exposure results in significant, long-lasting neurodevelopmental sequelae affecting sensory processing and behavior.
- These effects are mediated by direct actions of fentanyl on the developing brain, leading to distinct synaptic alterations in different cortical areas.
- The study highlights the critical need for understanding and mitigating the long-term consequences of prenatal opioid exposure.
Abstract:
One consequence of the opioid epidemic are lasting neurodevelopmental sequelae afflicting adolescents exposed to opioids in the womb. A translationally relevant and developmentally accurate preclinical model is needed to understand the behavioral, circuit, network, and molecular abnormalities resulting from this exposure. By employing a novel preclinical model of perinatal fentanyl exposure, our data reveal that fentanyl has several dose-dependent, developmental consequences to somatosensory function and behavior. Newborn male and female mice exhibit signs of withdrawal and sensory-related deficits that extend at least to adolescence. As fentanyl exposure does not affect dams' health or maternal behavior, these effects result from the direct actions of perinatal fentanyl on the pups' developing brain. At adolescence, exposed mice exhibit reduced adaptation to sensory stimuli, and a corresponding impairment in primary somatosensory (S1) function. In vitro electrophysiology demonstrates a long-lasting reduction in S1 synaptic excitation, evidenced by decreases in release probability, NMDA receptor-mediated postsynaptic currents, and frequency of miniature excitatory postsynaptic currents (mEPSCs), as well as increased frequency of miniature inhibitory postsynaptic currents (mIPSCs). In contrast, anterior cingulate cortical neurons exhibit an opposite phenotype, with increased synaptic excitation. Consistent with these changes, electrocorticograms (ECoGs) reveal suppressed ketamine-evoked γ oscillations. Morphologic analysis of S1 pyramidal neurons indicate reduced dendritic complexity, dendritic length, and soma size. Further, exposed mice exhibited abnormal cortical mRNA expression of key receptors involved in synaptic transmission and neuronal growth and development, changes that were consistent with the electrophysiological and morphologic changes. These findings demonstrate the lasting sequelae of perinatal fentanyl exposure on sensory processing and function.SIGNIFICANCE STATEMENT This is the first study to show that exposure to fentanyl in the womb results in behavioral, circuitry, and synaptic effects that last at least to adolescence. We also show, for the first time, that this exposure has different, lasting effects on synapses in different cortical areas.
