Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98721 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sickle cell disease is the most common genetic disorder in African-Americans. The opioid analgesic, morphine, has long been the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist, naloxone, possesses potent analgesic activity in two strains of sickle cell mice (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes. In the NY1DD sickle mice, naloxone (i.c.v.) possessed ~300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting that analgesia was mediated via different receptor systems. Since microarray analysis suggested naloxone-induced down-regulation of the CCR5 chemokine receptor in NY1DD mice but not in control mice, the role of its endogenous ligand, CCL5 (RANTES), was investigated. Keywords: Comparison of drug induced gene expression
2007-03-14 | GSE6578 | GEO
Project description:Sickle cell disease is the most common genetic disorder in African-Americans. The opioid analgesic, morphine, has long been the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist, naloxone, possesses potent analgesic activity in two strains of sickle cell mice (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes. In the NY1DD sickle mice, naloxone (i.c.v.) possessed ~300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting that analgesia was mediated via different receptor systems. Since microarray analysis suggested naloxone-induced down-regulation of the CCR5 chemokine receptor in NY1DD mice but not in control mice, the role of its endogenous ligand, CCL5 (RANTES), was investigated. Keywords: Comparison of drug induced gene expression
2007-12-20 | GSE6479 | GEO
Project description:Analgesia of naloxone in wild-type and NY1DD transgenic mouse model of sickle cell anemia using BMAP cDNA microarrays
| PRJNA98761 | ENA
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:Because opioid withdrawal is an intensely aversive experience, persons with opioid use disorder (OUD) often relapse to avoid it. The lateral septum (LS) is a forebrain structure that is important in aversion processing, and previous studies have linked the LS to substance use disorders. It is unclear, however, which precise LS cell types might contribute to the maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing to interrogate cell type specific gene expression changes induced by chronic morphine and withdrawal. We discovered that morphine globally disrupts the transcriptional profile of LS cell types, but neurotensin-expressing neurons (Nts; LS-Nts neurons) are selectively activated by naloxone. Using two-photon calcium imaging and ex vivo electrophysiology, we next demonstrated that LS-Nts neurons receive enhanced glutamatergic drive in morphine-dependent mice and remain hyperactivated during opioid withdrawal. Finally, we showed that activating and silencing LS-Nts neurons during opioid withdrawal regulates pain coping behaviors and sociability. Together, these results suggest that LS-Nts neurons are a key neural substrate involved in opioid withdrawal and establish the LS as a crucial regulator of adaptive behaviors, specifically pertaining to OUD.
2025-05-15 | GSE236007 | GEO
Project description:We analyzed time-dependent behavioral responses to morphine and naloxone obtained from a large family of young adult BXD mice (n = 63–64 strains, including C57BL/6J and DBA/2J parents, n = 4–9/strain) using new whole genome sequencing (WGS)-based genetic markers. Opiate behavioral data include locomotor and behavior responses measured over a four hour period in 15 min bins after an acute morphine injection (50 mg/kg i.p.), followed by naloxone-induced withdrawal (see Philip et al. (2010). Sexes were mapped jointly and independently for males and females using 20,000 markers and linear mixed models that account for kinship structure. We confirmed a highly significant association between locomotor response and a genomic region that overlaps Oprm1 on Chr 10 at 6.8 Mb (LOD of 11.4) 15 to 105 min after injection, with a peak at 75 min. Effects were only weakly dependent of sex. Strains that inherited B haplotypes ran 76 meters farther than those that inherited D haplotypes. We discovered a novel association between a locus on Chr 16 and a late-phase locomotor response 150 min after morphine in both sexes. This locus had a significant but transient epistatic interaction with Oprm1 at 45–90 min—well before its main additive effect was detectable. The Chr 16 locus includes one compelling candidate—fibroblast growth factor 12 (Fgf12). Null mutation of Fgf12 has been shown to cause locomotor deficits (e.g., ataxia). Single nuclei transcriptomic analysis further validated a functional epistatic relationship between Oprm1 and Fgf12, showing that their expression is correlated in a specific subtype of Drd1-expressing medium spiny neurons.
2023-09-27 | GSE214388 | GEO
Project description:Opioids are widely used, effective analgesics to manage severe acute and chronic pain, although they have recently come under scrutiny because of epidemic levels of abuse. While these compounds act on numerous central and peripheral pain pathways, the neuroanatomical substrate for opioid analgesia is not fully understood. By means of single-cell transcriptomics and manipulation of morphine-responsive neurons, have identified an ensemble of neurons in the rostral ventromedial medulla (RVM) that regulates mechanical nociception in mice. Among these, forced activation or silencing of excitatory RVMBDNF projection neurons mimicked or completely reversed morphine-induced mechanical antinociception, respectively, via a brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)-dependent mechanism and activation of inhibitory spinal galanin-positive neurons. Our results reveal a specific RVM-spinal circuit that scales mechanical nociception whose function confers the antinociceptive properties of morphine.
2024-08-30 | GSE253816 | GEO
Project description:Purpose: The goals of this study were to identify gene expression signatures that are unique to Tregs from mice upon treatments with smoke, morphine and smoke plus morphine Methods and results: Wild-type mice were treated with cigarette smoke (SM) for a period of eight weeks, and/or the chronic continuous administration of morphine (M) via mini-pumps for the final four weeks CD4+CD25highCD127low Tregs from spleen were purified by cell sorting to generate mRNA transcription. Transcriptional profiling revealed a unique Treg signatures in SM, M or SM + M relative to control mice. Conclusion: Our study represents the first detailed analysis of splenic Treg transcriptome in mice exposure to smoke plus morphine.
2022-04-14 | GSE198210 | GEO
Project description:This is a blinded randomized controlled trial in patients undergoing laparoscopic colon surgery. The aim of this study is to assess whether spinal analgesia with a mixture of bupivacaine and morphine provides better pain relief than systemic morphine in a group of patients undergoing colonic resection and using the Enhanced Recovery After Surgery (ERAS) program.
Twenty patients will receive spinal analgesia and twenty patients will receive only Patient Control Analgesia (PCA).
| 2116089 | ecrin-mdr-crc
Project description:Opioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. We have recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate the gut homeostasis. By using a mouse model of morphine treatment, we studied effects of morphine treatment on gut microbiome. We characterized phylogenetic profiles of gut microbes, and found a significant shift in the gut microbiome and increase of pathogenic bacteria following morphine treatment when compared to placebo. In the present study, wild type mice (C57BL/6J) were implanted with placebo, morphine pellets subcutaneously. Fecal matter were taken for bacterial 16s rDNA sequencing analysis at day 3 post treatment. A scatter plot based on an unweighted UniFrac distance matrics obtained from the sequences at OTU level with 97% similarity showed a distinct clustering of the community composition between the morphine and placebo treated groups. By using the chao1 index to evaluate alpha diversity (that is diversity within a group) and using unweighted UniFrac distance to evaluate beta diversity (that is diversity between groups, comparing microbial community based on compositional structures), we found that morphine treatment results in a significant decrease in alpha diversity and shift in fecal microbiome at day 3 post treatment compared to placebo treatment. Taxonomical analysis showed that morphine treatment results in a significant increase of potential pathogenic bacteria. Our study shed light on effects of morphine on the gut microbiome, and its role in the gut homeostasis.
2018-04-16 | E-MTAB-5546 | biostudies-arrayexpress