Perinatal Fentanyl Exposure Leads to Lasting Behavioral Vulnerabilities and Altered in the Central Amygdala in Rats
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1260456 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Opioid use during pregnancy is a growing public health concern, with in utero exposure to synthetic opioids like fentanyl linked to Neonatal Opioid Withdrawal Syndrome (NOWS) and long-term neurobehavioral impairments. However, the long-term neurodevelopmental consequences of in utero opioid exposure remain poorly understood. We developed a translationally relevant rat model of perinatal fentanyl exposure to investigate the behavioral and molecular outcomes of prenatal opioid exposure. Offspring born to fentanyl-exposed dams showed reduced survival rates, lower body weight, and spontaneous withdrawal symptoms. In adolescence, they displayed mechanical hypersensitivity and behaviors consistent with negative affect. In adulthood, these rats exhibited enhanced fentanyl self-administration, increased reinstatement behavior, and elevated plasma corticosterone levels during withdrawal. Furthermore, they showed increased risk-taking behavior in the Elevated Plus Maze, suggesting altered anxiety or impulsivity regulation. To investigate molecular correlates of these phenotypes, we performed transcriptomic profiling of the central amygdala of adult rats. Differential gene expression and gene set enrichment analyses revealed that perinatal fentanyl exposure led to dysregulation of pathways involved in synaptic signaling, neurodevelopment, GPCR signaling, and immune responses. These transcriptional changes provide a molecular framework for understanding how early fentanyl exposure leads to long-lasting vulnerability to stress and addiction-related behaviors. These findings underscore the lasting impact of perinatal opioid exposure on brain function and behavior and support the utility of this model for translational research on NOWS and opioid-related neuropsychiatric risk.
2025-06-27 | GSE296650 | GEO
Project description:Using bulk RNAseq, we explored transcriptomic landscape of three reward areas - PrL, NAc, VTA and two sensory areas -S1, VBT in perinatal fentanyl exposed juvenile mice
2023-05-08 | GSE231981 | GEO
Project description:Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increases in use of fentanyl; therefore, the identification of novel biomarkers and treatment strategies is critical. Here, we define how manipulations of the gut microbiome drive fentanyl intake, fentanyl seeking, and alter proteomic plasticity in the nucleus accumbens. These findings establish clear relevance for gut-brain signaling in OUD, and lay foundations for further translational work in this space.
2024-05-22 | PXD035810 | Pride
Project description:An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex. In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake.
2023-01-10 | GSE222569 | GEO
Project description:Background: Opioid withdrawal is a key driver of opioid addiction and an obstacle to recovery. However, withdrawal effects on opioid reinforcement and mesolimbic neuroadaptation are understudied and the role of sex is largely unknown. Methods: Male (n=13) and female (n=12) rats responded under a fentanyl-vs.-food “choice” procedure during daily 2h sessions. In addition to the daily choice sessions, rats were provided extended access to fentanyl during 12h self-administration sessions. After two weeks of this selfadministration regimen, the nucleus accumbens (NAc) and ventral tegmental area (VTA) of a subset of rats were subjected to RNA sequencing. In the remaining rats, a third week of this self-administration regimen was conducted, during which methadone effects on fentanyl-vs.-food choice were determined. Results: Prior to opioid dependence, male and female rats similarly allocated responding between fentanyl and food. Abstinence from extended fentanyl access elicited similar increases in somatic withdrawal signs in both sexes. Despite similar withdrawal signs and extended access fentanyl intake, opioid withdrawal was accompanied by a maladaptive increase in fentanyl choice in males, but not females. Behavioral sex differences corresponded with a greater number of differentially expressed genes in the NAc and VTA of opioidwithdrawn females relative to males. Methadone blocked withdrawal-associated increases in fentanyl choice in males, but failed to further decrease fentanyl choice in females. Conclusions: These results provide foundational evidence of sex-specific neuroadaptations to opioid withdrawal, which may be relevant to the female-specific resilience to withdrawal-associated increases in opioid choice and aid in the identification of novel therapeutic targets.
2021-05-06 | GSE173959 | GEO
Project description:Sex-specific transcriptomic profiling of reward and sensory brain areas in perinatal fentanyl exposed juvenile mice+G4
| PRJNA970351 | ENA
Project description:The opioid epidemic has introduced significant public health challenges with little knowledge regarding the consequences of opioid exposure during embryonic development. While neurobehavioral effects of developmental opioid exposure are well-documented, early effects of exposure remain largely unexplored. We investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (Oxycodone HCl 10.6pg/mL and Fentanyl Citrate 0.629pg/mL) and therapeutically relevant (Oxycodone HCl 35.14ng/mL and Fentanyl Citrate 3.14ng/mL) from 2 to 24 hours post-fertilization (hpf), followed by another 24hrs of opioid-free development. RNA sequencing at 48hpf revealed dose and drug specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed genes (DEGs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DEGs were identified across all conditions indicating continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include axon guidance, synapse formation, and ECM biosynthesis/remodeling all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that developmental exposure to opioids induced persistent transcriptomic changes which may have lasting implications for structural integrity and function in vertebrate nervous systems, providing insights into the molecular mechanisms of opioid-induced alterations during development.
2025-06-04 | GSE292183 | GEO
Project description:The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of syntheticopioids such as fentanyl. we evaluated the impact of fentanyl using in cell lines that replicate infectious viruses. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFkB signaling.
2021-04-21 | GSE167922 | GEO
Project description:Fentanyl enhanced expression of CXCR4 and CCR5 protein levels and viral expression in a dose-dependent manner in multiple HIV-susceptible and HIV-infected cell lines. Multiple genes associated with apoptosis, antiviral / interferon response, chemokine. signaling, and NFκB signaling were differentially regulated by fentanyl. Thus fentanyl impacts HIV replication and chemokine co-receptor expression in HIV-susceptible and HIV-infected lymphocyte cell lines suggesting that opioid use may increase the likelihood of transmission to others and accelerate disease progression.
2022-10-20 | GSE216124 | GEO
Project description:The illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis in the United States. People with opioid use disorder are more likely to contract infections such as HIV and viral hepatitis. While several drugs of abuse are known to enhance viral replication and to suppress immunologic responses, the effects of synthetic opioids on HIV pathogenesis have not been investigated thoroughly. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types and chemokine receptor expression in vitro. TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at concentrations of 1 ng, 100 ng, and 10 ug. Expression levels of the CXCR4 and CCR5 chemokine receptors were measured in cell lysates, and HIV p24 antigen was quantified in culture supernatants by ELISA. HIV proviral DNA was quantified in cells using SYBR RT-PCR targeting the pol gene. Cell viability in the presence of drug was detected by the MTT Cell Proliferation Assay. RNA-seq and miRNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Fentanyl enhanced expression of CXCR4 and CCR5 protein levels in a dose-dependent manner in HIV-susceptible and HIV-infected cells. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in multiple HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral / interferon response, chemokine signaling, and NFκB signaling were differentially regulated by fentanyl. These data demonstrate that the synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression in HIV-susceptible and HIV-infected cells. Increased virus levels also suggest that opioid use may increase the likelihood of transmission to others and accelerate disease progression.
2022-10-19 | GSE216044 | GEO