Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures
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ABSTRACT:
PROVIDER: PRJNA856310 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR20005966.fastq.gz | Fastqsanger.gz | |||
| SRR20005967.fastq.gz | Fastqsanger.gz | |||
| SRR20005968.fastq.gz | Fastqsanger.gz | |||
| SRR20005969.fastq.gz | Fastqsanger.gz | |||
| SRR20005970.fastq.gz | Fastqsanger.gz |
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Project description:It remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. We examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 µM) and high (10 µM) dose from primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte-lineage cell.
2022-08-31 | GSE207606 | GEO
Project description:Fentanyl is one of the most common opioid analgesics administered to patients undergoing surgery or for chronic pain management. While the side effects of chronic fentanyl abuse are recognized (e.g., addiction, tolerance, impairment of cognitive functions, and inhibit nociception, arousal, and respiration), it remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. Here, we examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 μM) and high (10 μM) dose. Primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte precursor cells, were seeded in wells on either a 6-well multi-electrode array (MEA, for electrophysiology) or a 96-well tissue culture plate (for serial endpoint bulk RNA sequencing analysis). Once networks matured (at 28 days in vitro), co-cultures were treated with 0.01 or 10 μM of fentanyl for 4 days and monitored daily. Only high dose exposure to fentanyl resulted in a decline in features of spiking and bursting activity as early as 30 min post-exposure and sustained for 4 days in cultures. Transcriptomic analysis of the complex cultures after 4 days of fentanyl exposure revealed that both the low and high dose induced gene expression changes involved in synaptic transmission, inflammation, and organization of the extracellular matrix. Collectively, the findings of this in vitro study suggest that while neuroadaptive changes to neural network activity at a systems level was detected only at the high dose of fentanyl, transcriptomic changes were also detected at the low dose conditions, suggesting that fentanyl rapidly elicits changes in plasticity.
| S-EPMC9403314 | biostudies-literature
Project description:The rise in synthetic opioid use, particularly fentanyl, has severely exacerbated the opioid epidemic and its impact surged dramatically during the COVID-19 pandemic. Fentanyl, a prescription opioid used for anesthesia and analgesia, is 50-100x stronger than morphine. Opioid-induced cardiac arrest represents the most dramatic manifestation of the opioid use disorder. Fentanyl primarily targets opioid receptors (ORs) in the nervous system, but its misuse also adversely depresses the pulmonary and cardiovascular systems. The proarrhythmic effects of other opioids were reported; however, the electrophysiological consequences of fentanyl abuse have not been studied. Our analysis of 19 toxicology studies conducted between 1994 and 2022 found that the average blood concentration of fentanyl in abuse or overdose cases is 30±1 ng/mL (89 nM), ~3-fold higher than in chronic pain or ~7.5-fold higher than in occasionally exposed patients. Advances in human induced pluripotent stem cell (iPSC) technology provide unprecedented opportunities to study patient‐specific responses to opioid abuse. Human iPSC-derived cardiomyocytes (iPSC-CMs) from 3 healthy donors were exposed to three doses of 89 nM fentanyl for 5 days. Then, we investigated whether fentanyl abuse has any consequences on cardiac electrophysiology.
2025-09-03 | GSE287796 | GEO
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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: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: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.
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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
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