{
  "abstract": "Mu opioid agonists, the most widely used opioids, produce analgesia, respiratory depression, constipation, and reward leading to substance abuse. Like all opioid receptor family members, mu receptors are Gi/o-coupled and inhibitory, yet mu-mediated disinhibition of GABAergic neurons propagates downstream activation that differs between naive and dependent animals and across receptor subtypes. Here we used TRAP2/Ai9 reporter mice, which deposit tdTomato in active neurons via the c-Fos locus, with tissue clearing and light sheet microscopy to map whole-brain neuronal activation after acute morphine (10 mg/kg), an escalating twice-daily morphine regimen producing dependence, or the NOP receptor agonist Ro 64-6198. Despite Gi/o coupling, all treatments raised global activation relative to vehicle, though this whole-brain increase reached significance only in males, and acute morphine engaged the largest number of regions, all increased with none decreased. Sex differences were prominent: males were more sensitive than females across treatments, with morphine engaging mainly pain- and reward-related midbrain circuitry in males and hypothalamic circuitry in females. In dependent mice, activation was lower across several regions, including a cluster of cerebellar regions that trended toward being turned off relative to acute morphine. NOP receptor activation produced a far weaker profile. Although chronic morphine produced less activation than acute morphine, it produced more widespread co-activation, and while hub composition differed across conditions, global network organization was preserved. These results reveal whole-brain changes in neuronal activation and establish a TRAP2/Ai9 model that renders activated regions genetically accessible for future site-directed investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Florida Atlantic University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "M. Martinez"
    },
    {
      "name": "A. Ozawa"
    },
    {
      "name": "D. Van Zant"
    },
    {
      "name": "J. Thornberry"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Toll"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/15m4p3ssvc80p.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753526",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753526v1.full",
  "id": "15m4p3ssvc80p",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753526v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2804|Neuropeptides and Animal Physiology"
    ]
  ],
  "openalex": "W7214646155",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753526v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/15m4p3ssvc80p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:58Z",
      "native_id": "10.64898/2026.09.22.753526",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753526v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Whole Brain Cellular Activation After Mu and NOP Receptor Agonism Identifies Differential Regional and Network Consequences",
  "title_text": "Whole Brain Cellular Activation After Mu and NOP Receptor Agonism Identifies Differential Regional and Network Consequences",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:58Z",
  "url": "https://research.draconitic.com/paper/15m4p3ssvc80p",
  "venue": "bioRxiv",
  "versions": []
}