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dc.contributor.authorRea, Kieran
dc.contributor.authorMcGowan, Fiona
dc.contributor.authorCorcoran, Louise
dc.contributor.authorRoche, Michelle
dc.contributor.authorFinn, David P.
dc.date.accessioned2019-04-03T09:04:19Z
dc.date.issued2018-05-30
dc.identifier.citationRea, Kieran, McGowan, Fiona, Corcoran, Louise, Roche, Michelle, & Finn, David P. (2018). The prefrontal cortical endocannabinoid system modulates fear–pain interactions in a subregion-specific manner. British Journal of Pharmacology, doi: 10.1111/bph.14376en_IE
dc.identifier.issn1476-5381
dc.identifier.urihttp://hdl.handle.net/10379/15093
dc.description.abstractBackground and Purpose The emotional processing and coordination of top‐down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC [infralimbic (IfL), prelimbic (PrL) and anterior cingulate (ACC) cortices] differentially alter the expression of contextually induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IfL, PrL and ACC in formalin‐evoked nociceptive behaviour, fear‐conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. Experimental Approach FCA was modelled in male Lister‐hooded rats by assessing formalin‐evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra‐mPFC administration of AM251 [cannabinoid type 1 (CB1) receptor antagonist/inverse agonist], URB597 [fatty acid amide hydrolase (FAAH) inhibitor] or URB597 + AM251 on FCA and freezing behaviour were assessed. Key Results AM251 attenuated FCA when injected into the IfL or PrL and reduced contextually induced freezing behaviour when injected intra‐IfL but not intra‐PrL or intra‐ACC. Intra‐ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra‐IfL, prolonged the expression of FCA when injected intra‐PrL and had no effect on these behaviours when injected intra‐ACC. Conclusions and Implications These results suggest important and differing roles for FAAH substrates or CB1 receptors in the PrL, IfL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone.en_IE
dc.description.sponsorshipThis work was funded by grants from the Science Foundation Ireland (10/IN.1/B2976), the Irish Research Council and a PhD scholarship from the College of Medicine, National University of Ireland Galway.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherWileyen_IE
dc.relation.ispartofBritish Journal Of Pharmacologyen
dc.subjectpainen_IE
dc.subjectfearen_IE
dc.subjectanxietyen_IE
dc.subjectcannabinoid1 (CB1) receptoren_IE
dc.subjectanandamideen_IE
dc.subjectfatty acid amide hydrolase (FAAH)en_IE
dc.subjectformalinen_IE
dc.subjectprefrontal cortexen_IE
dc.subjectstress-induced analgesiaen_IE
dc.titleThe prefrontal cortical endocannabinoid system modulates fear–pain interactions in a subregion‐specific manneren_IE
dc.typeArticleen_IE
dc.date.updated2019-03-28T08:35:10Z
dc.identifier.doi10.1111/bph.14376
dc.local.publishedsourcehttps://doi.org/10.1111/bph.14376en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderIrish Research Councilen_IE
dc.contributor.funderCollege of Medicine, National University of Ireland Galwayen_IE
dc.description.embargo2019-05-30
dc.internal.rssid16097320
dc.local.contactDavid Finn, Dept. Of Pharmacology &, Therapeutics, Nui, Galway. 5280 Email: david.finn@nuigalway.ie
dc.local.copyrightcheckedyes
dc.local.versionACCEPTED
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/10/IN.1/B2976/IE/The role of the endocannabinoid system in anxiety-induced modulation of pain: sites and mechanisms of action/en_IE
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