{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:07:25Z","timestamp":1768734445706,"version":"3.49.0"},"reference-count":89,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["207530\/2014-9"],"award-info":[{"award-number":["207530\/2014-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["10\/IN.1\/B2976"],"award-info":[{"award-number":["10\/IN.1\/B2976"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is evidence for the involvement of peroxisome proliferator-activated receptors (PPARs) in pain, cognition, and anxiety. However, their role in pain\u2013fear interactions is unknown. The amygdala plays a key role in pain, conditioned fear, and fear-conditioned analgesia (FCA). We investigated the effects of intra-basolateral amygdala (BLA) administration of PPAR\u03b1, PPAR\u03b2\/\u03b4, and PPAR\u03b3 antagonists on nociceptive behaviour, FCA, and conditioned fear in the presence or absence of nociceptive tone. Male Sprague-Dawley (SD) rats received footshock (FC) or no footshock (NFC) in a conditioning arena. Twenty-three and a half hours later, rats received an intraplantar injection of formalin or saline and, 15 min later, intra-BLA microinjections of vehicle, PPAR\u03b1 (GW6471) PPAR\u03b2\/\u03b4 (GSK0660), or PPAR\u03b3 (GW9662) antagonists before arena re-exposure. Pain and fear-related behaviour were assessed, and neurotransmitters\/endocannabinoids measured post-mortem. Intra-BLA administration of PPAR\u03b1 or PPAR\u03b3 antagonists potentiated freezing in the presence of nociceptive tone. Blockade of all PPAR subtypes in the BLA increased freezing and BLA dopamine levels in NFC rats in the absence of nociceptive tone. Administration of intra-BLA PPAR\u03b1 and PPAR\u03b3 antagonists increased levels of dopamine in the BLA compared with the vehicle-treated counterparts. In conclusion, PPAR\u03b1 and PPAR\u03b3 in the BLA play a role in the expression or extinction of conditioned fear in the presence or absence of nociceptive tone.<\/jats:p>","DOI":"10.3390\/molecules27062021","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T21:48:42Z","timestamp":1647899322000},"page":"2021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of Intra-BLA Administration of PPAR Antagonists on Formalin-Evoked Nociceptive Behaviour, Fear-Conditioned Analgesia, and Conditioned Fear in the Presence or Absence of Nociceptive Tone in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0227-5449","authenticated-orcid":false,"given":"Jessica C.","family":"Gaspar","sequence":"first","affiliation":[{"name":"Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bright N.","family":"Okine","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dinneen","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Physiology, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-9397","authenticated-orcid":false,"given":"Michelle","family":"Roche","sequence":"additional","affiliation":[{"name":"Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Physiology, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-621X","authenticated-orcid":false,"given":"David P.","family":"Finn","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/347645a0","article-title":"Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators","volume":"347","author":"Issemann","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejphar.2015.11.004","article-title":"Fatty acids, eicosanoids and PPAR gamma","volume":"785","author":"Savoye","year":"2016","journal-title":"Eur. 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