Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception
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ABSTRACT:
PROVIDER: PRJNA731899 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14615071_1.fastq.gz | Fastqsanger.gz | |||
| SRR14615071_2.fastq.gz | Fastqsanger.gz | |||
| SRR14615072_1.fastq.gz | Fastqsanger.gz | |||
| SRR14615072_2.fastq.gz | Fastqsanger.gz | |||
| SRR14615073_1.fastq.gz | Fastqsanger.gz |
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Project description:Preclinical studies suggest that parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal morphine exposure on sensitivity to morphine-derived antinociception in offspring. We developed a novel sub-second pain scale with statistical modeling and machine learning to measure mechanical nociception in Long Evans and Sprague Dawley male and female rats. Next, we used this rat pain scale with a multigenerational paternal morphine exposure paradigm to determine whether chronic paternal morphine exposure impacts pain sensitivity in offspring. Finally, we used RNA sequencing to identify potential molecular correlates of sire exposure to morphine on offspring. Surprisingly, we found that von Frey hair filaments (VFHs), the most commonly-used noxious mechanical stimuli to test pain sensitivity, are not painful to rats as measured by this novel rat pain scale. Male progeny produced from morphine-treated sires did not exhibit any baseline changes in sensitivity to noxious mechanical stimuli but had greater sensitivity to the antinociceptive properties of morphine. Changes in gene expression within the periaqueductal gray, including primary members of the RGS family of proteins, were identified that may play a role in modified sensitivity to morphine within offspring. These findings reveal nuanced responses to VFHs that should be considered in future pain studies and demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent male generation.
2025-05-20 | GSE174846 | GEO
Project description:Parental history of opioid exposure is seldom considered when prescribing opioids for pain relief. To explore whether parental opioid exposure may affect sensitivity to morphine in offspring, we developed a "rat pain scale" with high-speed imaging, machine learning, and mathematical modeling in a multigenerational model of paternal morphine self-administration. We find that the most commonly used tool to measure mechanical sensitivity in rodents, the von Frey hair, is not painful in rats during baseline conditions. We also find that male progeny of morphine-treated sires had no baseline changes in mechanical pain sensitivity but were more sensitive to the pain-relieving effects of morphine. Using RNA sequencing across pain-relevant brain regions, we identify gene expression changes within the regulator of G protein signaling family of proteins that may underlie this multigenerational phenotype. Together, this rat pain scale revealed that paternal opioid exposure increases sensitivity to morphine's pain-relieving effects in male offspring.
| S-EPMC8849295 | biostudies-literature
Project description:A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS. Our study identified different functional classes of genes and individual candidates involved in the mechanisms underlying susceptibility to morphine actions related to CNS development. These results open new lines to study the treatment of pain and the molecular mechanisms involved in addiction. We also found a set of zebrafish-specific morphine-induced genes, which may be putative targets in human models for addiction and pain processes. Zebrafish embryos were divided into two experimental groups: control embryos and embryos at 5 hpf exposed to 10 nM morphine and collected at 24 hpf (covering the complete embryogenesis). Morphine was administered to the embryos in their water environment, i.e., diluted in E3 embryonic medium. The exposition to begun at the stage of 5 hpf (end of blastula) is continuous, in order to study the chronic effects of the exposure to drug. Microarray experiments were performed using six replicates for each condition, which contained the RNA of approximately one hundred embryos to minimize the influence of potential individual differences between the animals and technical variation introduced by tissue preparation. We previously reported that a concentration of 10 nM morphine is the highest concentration that can be used without a toxic effect on the embryos, and close to 5% of the morphine diluted in the E3 medium is detected in the embryo.
2014-09-04 | E-GEOD-61062 | biostudies-arrayexpress
Project description:We examined the impact of paternal abstinence following morphine self_administration on the transmission of multigenerational factors from the F0 to the F1 generation. Previously, we found that offspring of non_abstinent, morphine administering male rats showed increased morphine_taking, diminished adolescent social play, and reduced sensitivity to morphine analgesia. Here, we show that these phenotypes are normalized in the offspring of fathers who were 90 days abstinent from morphine at the time of breeding. We further compared the small RNA content of sperm collected from non_abstinent versus 90 days abstinent F0 males to identify candidate molecules correlated with transmission of morphine_induced multigenerational phenotypes.
2025-05-30 | GSE274906 | GEO
Project description:Morphine addiction causes major medical and social problems worldwide. Chronic morphine exposure results in the development of behavioral sensitization, accompanied by the disruption of brain homeostasis. As a key brain reward region, nucleus accumbens (NAc) plays a central role in brain reward mechanisms. However, the contribution of morphine exposure to NAc is poorly understood. Here we indicated that chronic morphine exposure induced neuroinflammation, abnormal neuronal physiology, and dysregulation of glycolytic metabolism in NAc. In summary, our findings illustrate the effects of morphine in NAc, and provide a new insight for development of future morphine addiction therapeutics.
2023-07-28 | GSE239387 | GEO
Project description:A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS. Our study identified different functional classes of genes and individual candidates involved in the mechanisms underlying susceptibility to morphine actions related to CNS development. These results open new lines to study the treatment of pain and the molecular mechanisms involved in addiction. We also found a set of zebrafish-specific morphine-induced genes, which may be putative targets in human models for addiction and pain processes.
2014-09-04 | GSE61062 | GEO
Project description:Chronic morphine exposure to rhesus macaque
2023-11-28 | GSE233278 | GEO
Project description:Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR gene expression. C57BL/6 male mice were treated from postnatal day (P) 5 to P9 with morphine at 2 or 5 mg/kg ip bid (MS5) and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min) followed by 2h maternal separation. Control mice were untreated and dam-reared. mRNA and microRNA expression profiling was performed on hippocampal tissues at P9. Overall, MS2 and MS5 morphine treatment altered expression of a total of 150 mRNAs (>1.5 fold change, P<0.05; 36 up, 114 down), and MS5 affected 63 mRNAs. The most upregulated mRNAs were fidgetin, arginine vasopressin, and resistin-like alpha, and the most down-regulated were defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel 6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment affected pathways related to cell cycle, membrane function, signaling, metabolism, cell death, transcriptional regulation, and immune response. MS5 decreased expression of miR-204-5p, miR-455-3p, miR-448-3p, and miR-574-3p.Nine morphine-responsive mRNAs that are involved in neurodevelopment, neurotransmission, and inflammation are predicted targets of the aforementioned differentially expressed microRNAs These data establish that morphine produces dose-dependent changes in both hippocampal mRNA and miR gene expression in stressed neonatal mice. If permanent, morphine–mediated neuroepigenetic effects may affect long-term hippocampal function, and this provides a mechanism for the neonatal morphine-related impairment of adult learning.
2015-10-05 | GSE62346 | GEO
Project description:Epigenetic changes are essential for normal development and ageing, but there is still limited understanding of how environmental factors can cause epigenetic changes that leads to health problems or diseases. Morphine is known to pass through the placental barrier and impact normal embryo development by affecting the neural tube, frontal cortex and spinal cord development, and, as a consequence, delaying nervous system development. In fact, in-utero morphine exposure has shown alterations in anxiety-like behaviours, analgesic tolerance, synaptic plasticity and the neuronal structure of offspring. However, how morphine leads to abnormal neurogenesis and other physiological consequences during embryo development is still unknown. Considering that DNA methylation is a key epigenetic factor crucial for embryo development, our aim is to elucidate the role of methylation in response to morphine. Chronic morphine treatment (24h, 10μM) induces a global hypomethylation in mESC. WGBSeq identifies 16,808 sensitive to morphine which are involved in embryo development, signalling pathways, metabolism and/or gene expression, suggesting that morphine might impact methylation levels at developmental genes. Integrative analyses between WGBSeq and RNASeq identified Tet1 as morphine-sensitive gene. Morphine increased the gene expression of Tet1, modifying the methylation levels at the promoter. On the other hand, RNASeq and qRT-PCR analyses revealed that Dnmt1 gene expression decreased after morphine treatment, without altering the methylation patter at its promoters. By MS/MS approaches confirms a decrease in DNA methylation after chronic morphine treatment, together with an increase in hydroxymethylation global levels in mESCs. In conclusion, morphine induces a global hypomethylation in mESC through different mechanisms that involves passive demethylation and a self-regulatory mechanism via active demethylation.
2025-03-21 | GSE292082 | GEO
Project description:Inhibiting phosphatidylcholine remodeling in adipose tissue increases insulin sensitivity
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