Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.

dc.citation.issue23
dc.citation.volume25
dc.contributor.authorParkar N
dc.contributor.authorYoung W
dc.contributor.authorOlson T
dc.contributor.authorHurst C
dc.contributor.authorJanssen P
dc.contributor.authorSpencer NJ
dc.contributor.authorMcNabb WC
dc.contributor.authorDalziel JE
dc.contributor.editorSzumlinski KK
dc.contributor.editorShiina T
dc.coverage.spatialSwitzerland
dc.date.accessioned2025-01-28T18:37:52Z
dc.date.available2025-01-28T18:37:52Z
dc.date.issued2024-12-07
dc.description.abstractAlthough effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood.
dc.description.confidentialfalse
dc.edition.editionDecember-1 2024
dc.format.pagination13183-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/39684893
dc.identifier.citationParkar N, Young W, Olson T, Hurst C, Janssen P, Spencer NJ, McNabb WC, Dalziel JE. (2024). Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.. Int J Mol Sci. 25. 23. (pp. 13183-).
dc.identifier.doi10.3390/ijms252313183
dc.identifier.eissn1422-0067
dc.identifier.elements-typejournal-article
dc.identifier.issn1661-6596
dc.identifier.number13183
dc.identifier.piiijms252313183
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/72423
dc.languageeng
dc.publisherMDPI (Basel, Switzerland)
dc.publisher.urihttp://mdpi.com/1422-0067/25/23/13183
dc.relation.isPartOfInt J Mol Sci
dc.rights(c) 2024 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectamygdala
dc.subjectcolon
dc.subjectdepression
dc.subjectenteric nervous system
dc.subjectgut–brain axis
dc.subjecthippocampus
dc.subjectloperamide
dc.subjectmicrobiota
dc.subjectAnimals
dc.subjectMale
dc.subjectFemale
dc.subjectAnxiety
dc.subjectRats
dc.subjectLoperamide
dc.subjectBrain
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Opioid
dc.subjectBehavior, Animal
dc.subjectGastrointestinal Microbiome
dc.subjectHippocampus
dc.subjectEnteric Nervous System
dc.subjectGene Expression Regulation
dc.subjectSex Factors
dc.subjectSex Characteristics
dc.titlePeripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.
dc.typeJournal article
pubs.elements-id492803
pubs.organisational-groupOther
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