{"id":"https://openalex.org/W7214646155","doi":"https://doi.org/10.64898/2026.09.22.753526","title":"Whole Brain Cellular Activation After Mu and NOP Receptor Agonism Identifies Differential Regional and Network Consequences","display_name":"Whole Brain Cellular Activation After Mu and NOP Receptor Agonism Identifies Differential Regional and Network Consequences","publication_year":2026,"publication_date":"2026-09-28","ids":{"openalex":"https://openalex.org/W7214646155","doi":"https://doi.org/10.64898/2026.09.22.753526","pmid":"https://pubmed.ncbi.nlm.nih.gov/42856102","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13648335"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.22.753526","doi":"https://doi.org/10.64898/2026.09.22.753526","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.22.753526","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.64898/2026.09.22.753526","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5032516617","display_name":"Madeline Martinez","orcid":"https://orcid.org/0000-0002-3756-0365","observed_orcids":["https://orcid.org/0000-0002-3756-0365"]},"institutions":[{"id":"https://openalex.org/I63772739","display_name":"Florida Atlantic University","ror":"https://ror.org/05p8w6387","country_code":"US","type":"education","lineage":["https://openalex.org/I63772739"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Madeline Martinez","raw_affiliation_strings":["Florida Atlantic University"],"raw_orcid":"https://orcid.org/0000-0002-3756-0365","affiliations":[{"raw_affiliation_string":"Florida Atlantic University","institution_ids":["https://openalex.org/I63772739"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021023227","display_name":"Akihiko Ozawa","orcid":"https://orcid.org/0000-0002-4471-7076","observed_orcids":["https://orcid.org/0000-0002-4471-7076"]},"institutions":[{"id":"https://openalex.org/I63772739","display_name":"Florida Atlantic University","ror":"https://ror.org/05p8w6387","country_code":"US","type":"education","lineage":["https://openalex.org/I63772739"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Akihiko Ozawa","raw_affiliation_strings":["Florida Atlantic University"],"raw_orcid":"https://orcid.org/0000-0002-4471-7076","affiliations":[{"raw_affiliation_string":"Florida Atlantic University","institution_ids":["https://openalex.org/I63772739"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5140178872","display_name":"Daniel Van Zant","orcid":"https://orcid.org/0009-0000-4455-7132","observed_orcids":["https://orcid.org/0009-0000-4455-7132"]},"institutions":[{"id":"https://openalex.org/I63772739","display_name":"Florida Atlantic University","ror":"https://ror.org/05p8w6387","country_code":"US","type":"education","lineage":["https://openalex.org/I63772739"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel Van Zant","raw_affiliation_strings":["Florida Atlantic University"],"raw_orcid":"https://orcid.org/0009-0000-4455-7132","affiliations":[{"raw_affiliation_string":"Florida Atlantic University","institution_ids":["https://openalex.org/I63772739"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5128351883","display_name":"Jake Thornberry","orcid":"https://orcid.org/0009-0003-9385-6907","observed_orcids":["https://orcid.org/0009-0003-9385-6907"]},"institutions":[{"id":"https://openalex.org/I63772739","display_name":"Florida Atlantic University","ror":"https://ror.org/05p8w6387","country_code":"US","type":"education","lineage":["https://openalex.org/I63772739"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jake Thornberry","raw_affiliation_strings":["Florida Atlantic University"],"raw_orcid":"https://orcid.org/0009-0003-9385-6907","affiliations":[{"raw_affiliation_string":"Florida Atlantic University","institution_ids":["https://openalex.org/I63772739"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5020423575","display_name":"Lawrence Toll","orcid":"https://orcid.org/0000-0002-4501-7573","observed_orcids":["https://orcid.org/0000-0002-4501-7573"]},"institutions":[{"id":"https://openalex.org/I63772739","display_name":"Florida Atlantic University","ror":"https://ror.org/05p8w6387","country_code":"US","type":"education","lineage":["https://openalex.org/I63772739"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Lawrence Toll","raw_affiliation_strings":["Florida Atlantic University"],"raw_orcid":"https://orcid.org/0000-0002-4501-7573","affiliations":[{"raw_affiliation_string":"Florida Atlantic University","institution_ids":["https://openalex.org/I63772739"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5020423575"],"corresponding_institution_ids":["https://openalex.org/I63772739"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.9106000065803528,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.9106000065803528,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10056","display_name":"Neurotransmitter Receptor Influence on Behavior","score":0.03889999911189079,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.024800000712275505,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/mu-opioid-receptor","display_name":"mu-opioid receptor","score":0.9359999895095825},{"id":"https://openalex.org/keywords/nop-receptor","display_name":"NOP receptor","score":0.8999999761581421},{"id":"https://openalex.org/keywords/morphine","display_name":"morphine","score":0.6769999861717224},{"id":"https://openalex.org/keywords/opioid-use-disorder","display_name":"opioid use disorder","score":0.9150000214576721},{"id":"https://openalex.org/keywords/neuronal-activation","display_name":"neuronal activation","score":0.8059999942779541},{"id":"https://openalex.org/keywords/sex-differences","display_name":"sex differences","score":0.7559999823570251},{"id":"https://openalex.org/keywords/brain-network-organization","display_name":"brain network organization","score":0.5540000200271606},{"id":"https://openalex.org/keywords/network-hubs","display_name":"network hubs","score":0.5},{"id":"https://openalex.org/keywords/gabaergic-disinhibition","display_name":"GABAergic disinhibition","score":0.671999990940094},{"id":"https://openalex.org/keywords/cerebellum","display_name":"cerebellum","score":0.6200000047683716},{"id":"https://openalex.org/keywords/hypothalamus","display_name":"hypothalamus","score":0.8140000104904175},{"id":"https://openalex.org/keywords/chronic-opioid-exposure","display_name":"chronic opioid exposure","score":0.4519999921321869}],"concepts":[{"id":"https://openalex.org/C159023312","wikidata":"https://www.wikidata.org/wiki/Q409513","display_name":"NOP","level":3,"score":0.9096999764442444},{"id":"https://openalex.org/C14397066","wikidata":"https://www.wikidata.org/wiki/Q14911924","display_name":"\u03bc-opioid receptor","level":4,"score":0.5875999927520752},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.5800999999046326},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.5476999878883362},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5303000211715698},{"id":"https://openalex.org/C2779886867","wikidata":"https://www.wikidata.org/wiki/Q421797","display_name":"Opioid receptor","level":4,"score":0.49720001220703125},{"id":"https://openalex.org/C2781063702","wikidata":"https://www.wikidata.org/wiki/Q427523","display_name":"Opioid","level":3,"score":0.4821000099182129},{"id":"https://openalex.org/C2777389121","wikidata":"https://www.wikidata.org/wiki/Q81225","display_name":"Morphine","level":2,"score":0.476500004529953},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4740000069141388},{"id":"https://openalex.org/C74254510","wikidata":"https://www.wikidata.org/wiki/Q7240508","display_name":"Premovement neuronal activity","level":2,"score":0.4724000096321106},{"id":"https://openalex.org/C2779177108","wikidata":"https://www.wikidata.org/wiki/Q18356742","display_name":"GABAergic","level":3,"score":0.44679999351501465},{"id":"https://openalex.org/C2776599063","wikidata":"https://www.wikidata.org/wiki/Q5282244","display_name":"Disinhibition","level":2,"score":0.4018999934196472},{"id":"https://openalex.org/C2776401185","wikidata":"https://www.wikidata.org/wiki/Q5204254","display_name":"DAMGO","level":5,"score":0.40049999952316284},{"id":"https://openalex.org/C2779715522","wikidata":"https://www.wikidata.org/wiki/Q507027","display_name":"Forebrain","level":3,"score":0.3824999928474426},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3734999895095825},{"id":"https://openalex.org/C552161191","wikidata":"https://www.wikidata.org/wiki/Q185080","display_name":"Midbrain","level":3,"score":0.37279999256134033},{"id":"https://openalex.org/C88016717","wikidata":"https://www.wikidata.org/wiki/Q417189","display_name":"Opioid peptide","level":4,"score":0.3587999939918518},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3560999929904938},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.35519999265670776},{"id":"https://openalex.org/C125439840","wikidata":"https://www.wikidata.org/wiki/Q14911984","display_name":"Nociceptin receptor","level":5,"score":0.33809998631477356},{"id":"https://openalex.org/C2779555244","wikidata":"https://www.wikidata.org/wiki/Q409638","display_name":"Immediate early gene","level":4,"score":0.33809998631477356},{"id":"https://openalex.org/C2777803847","wikidata":"https://www.wikidata.org/wiki/Q325101","display_name":"Enkephalin","level":4,"score":0.32670000195503235},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3149000108242035},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.31130000948905945},{"id":"https://openalex.org/C137183658","wikidata":"https://www.wikidata.org/wiki/Q461076","display_name":"Dopaminergic","level":3,"score":0.3082999885082245},{"id":"https://openalex.org/C43587935","wikidata":"https://www.wikidata.org/wiki/Q1258877","display_name":"Functional selectivity","level":4,"score":0.3070000112056732},{"id":"https://openalex.org/C2777688879","wikidata":"https://www.wikidata.org/wiki/Q904550","display_name":"Urocortin","level":3,"score":0.28279998898506165},{"id":"https://openalex.org/C8439214","wikidata":"https://www.wikidata.org/wiki/Q417749","display_name":"Autoreceptor","level":4,"score":0.27309998869895935},{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.2694999873638153},{"id":"https://openalex.org/C2777003273","wikidata":"https://www.wikidata.org/wiki/Q164386","display_name":"Hypothalamus","level":2,"score":0.2574999928474426}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.64898/2026.09.22.753526","doi":"https://doi.org/10.64898/2026.09.22.753526","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.22.753526","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},{"id":"pmid:42856102","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42856102","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv : the preprint server for biology","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13648335","doi":null,"is_oa":true,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42856102/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"bioRxiv","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.64898/2026.09.22.753526","doi":"https://doi.org/10.64898/2026.09.22.753526","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.22.753526","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G4168778688","display_name":"Dissecting active neural circuits regulating sensory and affective pain","funder_award_id":"R34NS121875","funder_id":"https://openalex.org/F4320337359","funder_display_name":"National Institute of Neurological Disorders and Stroke"},{"id":"https://openalex.org/G7093686701","display_name":"MIXED NOP/MU COMPOUNDS AND THE INVOLVEMENT OF THEIR RECEPTORS IN ANALGESIA","funder_award_id":"R01DA023281","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"}],"funders":[{"id":"https://openalex.org/F4320337347","display_name":"National Institute on Drug Abuse","ror":"https://ror.org/00fq5cm18"},{"id":"https://openalex.org/F4320337359","display_name":"National Institute of Neurological Disorders and Stroke","ror":"https://ror.org/01s5ya894"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":1,"referenced_works":["https://openalex.org/W2232667923"],"related_works":["https://openalex.org/W2037917849","https://openalex.org/W1585650753","https://openalex.org/W2079708017","https://openalex.org/W2122530393","https://openalex.org/W2921247428","https://openalex.org/W1969455171","https://openalex.org/W2078869722","https://openalex.org/W2022106862","https://openalex.org/W2355504992","https://openalex.org/W1971846106"],"abstract_inverted_index":{"Mu":[0],"opioid":[1,21],"agonists,":[2],"the":[3,64,92,122],"most":[4],"widely":[5],"used":[6,53],"opioids,":[7],"produce":[8],"analgesia,":[9],"respiratory":[10],"depression,":[11],"constipation,":[12],"and":[13,29,44,47,70,118,149,155,207,227],"reward":[14],"leading":[15],"to":[16,74,107,182],"substance":[17],"abuse.":[18],"Like":[19],"all":[20,101,127],"receptor":[22,49,94,186],"family":[23],"members,":[24],"mu":[25],"receptors":[26],"are":[27],"Gi/o-coupled":[28],"inhibitory,":[30],"yet":[31],"mu-mediated":[32],"disinhibition":[33],"of":[34,125,172],"GABAergic":[35],"neurons":[36,62],"propagates":[37],"downstream":[38],"activation":[39,78,105,163,187,198,226],"that":[40,175,232],"differs":[41],"between":[42],"naive":[43],"dependent":[45,161],"animals":[46],"across":[48,142,166,212],"subtypes.":[50],"Here":[51],"we":[52],"TRAP2/Ai9":[54,230],"reporter":[55],"mice,":[56,162],"which":[57],"deposit":[58],"tdTomato":[59],"in":[60,116,153,158,224],"active":[61],"via":[63],"c-Fos":[65],"locus,":[66],"with":[67,129,144],"tissue":[68],"clearing":[69],"light":[71],"sheet":[72],"microscopy":[73],"map":[75],"whole-brain":[76,111,222],"neuronal":[77,225],"after":[79],"acute":[80,119,183,200],"morphine":[81,87,120,145,195],"(10":[82],"mg/kg),":[83],"an":[84],"escalating":[85],"twice-daily":[86],"regimen":[88],"producing":[89],"dependence,":[90],"or":[91],"NOP":[93,185],"agonist":[95],"Ro":[96],"64-6198.":[97],"Despite":[98],"Gi/o":[99],"coupling,":[100],"treatments":[102],"raised":[103],"global":[104,214],"relative":[106,181],"vehicle,":[108],"though":[109],"this":[110],"increase":[112],"reached":[113],"significance":[114],"only":[115],"males,":[117],"engaged":[121],"largest":[123],"number":[124],"regions,":[126,168],"increased":[128],"none":[130],"decreased.":[131],"Sex":[132],"differences":[133],"were":[134,137],"prominent:":[135],"males":[136,154],"more":[138,204],"sensitive":[139],"than":[140,199],"females":[141],"treatments,":[143],"engaging":[146],"mainly":[147],"pain-":[148],"reward-related":[150],"midbrain":[151],"circuitry":[152,157],"hypothalamic":[156],"females.":[159],"In":[160],"was":[164,217],"lower":[165],"several":[167],"including":[169],"a":[170,189,229],"cluster":[171],"cerebellar":[173],"regions":[174,235],"trended":[176],"toward":[177],"being":[178],"turned":[179],"off":[180],"morphine.":[184],"produced":[188,196,203],"far":[190],"weaker":[191],"profile.":[192],"Although":[193],"chronic":[194],"less":[197],"morphine,":[201],"it":[202],"widespread":[205],"co-activation,":[206],"while":[208],"hub":[209],"composition":[210],"differed":[211],"conditions,":[213],"network":[215],"organization":[216],"preserved.":[218],"These":[219],"results":[220],"reveal":[221],"changes":[223],"establish":[228],"model":[231],"renders":[233],"activated":[234],"genetically":[236],"accessible":[237],"for":[238],"future":[239],"site-directed":[240],"investigation.":[241]},"counts_by_year":[],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2026-09-29T00:00:00"}