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Updated: Jul 24, 2025
Comprehensive Analysis of Transcription Dynamics from Brain Samples Following Behavioral Experience
Published on: August 26, 2014
Transcriptomic profiling of reward and sensory brain areas in perinatal fentanyl exposed juvenile mice
Jimmy Olusakin1,2, Gautam Kumar1,2, Mahashweta Basu3
1Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Insights
Perinatal fentanyl exposure alters brain gene expression in juvenile mice, with distinct molecular changes in reward and sensory areas between sexes. These changes may explain observed behavioral disruptions.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Fentanyl use has surged, particularly among women of reproductive age.
- Perinatal opioid exposure is linked to adverse neonatal and long-term behavioral outcomes.
- Previous studies showed adolescent behavioral and circuit disruptions in mice exposed to fentanyl during development.
Purpose of the Study:
- To investigate molecular adaptations in brain regions following perinatal fentanyl exposure.
- To identify sex-specific transcriptional changes in reward and sensory circuits.
- To understand the molecular basis for observed behavioral alterations.
Main Methods:
- Pregnant mice received fentanyl in drinking water from embryonic day 0 to postnatal day 21.
- RNA sequencing was performed on brain regions (nucleus accumbens, prelimbic cortex, ventral tegmental area, somatosensory cortex, ventrobasal thalamus) of juvenile offspring (postnatal day 35).
- Analysis included differentially expressed genes (DEGs) and gene co-expression networks, with sex-specific comparisons.
Main Results:
- Significant sex-specific differentially expressed genes and gene modules were identified in response to perinatal fentanyl.
- The ventral tegmental area showed the most DEGs; nucleus accumbens exhibited robust gene enrichment.
- Males showed enrichment in mitochondrial respiration and extracellular matrix/neuronal migration genes (NAc, VTA). Females displayed altered vesicular cycling/synaptic signaling (NAc) and mitochondrial respiration/synaptic/ciliary organization (sensory areas).
Conclusions:
- Perinatal fentanyl exposure induces distinct transcriptomic changes across reward and sensory brain regions.
- Sex-specific molecular adaptations were observed, suggesting differential vulnerability and outcomes.
- These transcriptome alterations likely contribute to the structural, functional, and behavioral changes seen in developing mice exposed to fentanyl.
Abstract:
Use of the synthetic opioid fentanyl increased ~300% in the last decade, including among women of reproductive ages. Adverse neonatal outcomes and long-term behavioral disruptions are associated with perinatal opioid exposure. Our previous work demonstrated that perinatal fentanyl exposed mice displayed enhanced negative affect and somatosensory circuit and behavioral disruptions during adolescence. However, little is known about molecular adaptations across brain regions that underlie these outcomes. We performed RNA sequencing across three reward and two sensory brain areas to study transcriptional programs in perinatal fentanyl exposed juvenile mice. Pregnant dams received 10 μg/ml fentanyl in the drinking water from embryonic day 0 (E0) through gestational periods until weaning at postnatal day 21 (P21). RNA was extracted from nucleus accumbens (NAc), prelimbic cortex (PrL), ventral tegmental area (VTA), somatosensory cortex (S1) and ventrobasal thalamus (VBT) from perinatal fentanyl exposed mice of both sexes at P35. RNA sequencing was performed, followed by analysis of differentially expressed genes (DEGs) and gene co-expression networks. Transcriptome analysis revealed DEGs and gene modules significantly associated with exposure to perinatal fentanyl in a sex-wise manner. The VTA had the most DEGs, while robust gene enrichment occurred in NAc. Genes enriched in mitochondrial respiration were pronounced in NAc and VTA of perinatal fentanyl exposed males, extracellular matrix (ECM) and neuronal migration enrichment were pronounced in NAc and VTA of perinatal fentanyl exposed males, while genes associated with vesicular cycling and synaptic signaling were markedly altered in NAc of perinatal fentanyl exposed female mice. In sensory areas from perinatal fentanyl exposed females, we found alterations in mitochondrial respiration, synaptic and ciliary organization processes. Our findings demonstrate distinct transcriptomes across reward and sensory brain regions, with some showing discordance between sexes. These transcriptome adaptations may underlie structural, functional, and behavioral changes observed in perinatal fentanyl exposed mice.
