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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
Authors:Jessica C Gaspar  Bright N Okine  David Dinneen  Michelle Roche  David P Finn
Institution:1.Pharmacology and Therapeutics, National University of Ireland Galway, H91 W5P7 Galway, Ireland; (J.C.G.); (B.N.O.); (D.D.);2.Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland;3.Centre for Pain Research, National University of Ireland Galway, H91 W5P7 Galway, Ireland;4.Physiology, National University of Ireland Galway, H91 W5P7 Galway, Ireland
Abstract:There is evidence for the involvement of peroxisome proliferator-activated receptors (PPARs) in pain, cognition, and anxiety. However, their role in pain–fear 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 PPARα, PPARβ/δ, and PPARγ 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, PPARα (GW6471) PPARβ/δ (GSK0660), or PPARγ (GW9662) antagonists before arena re-exposure. Pain and fear-related behaviour were assessed, and neurotransmitters/endocannabinoids measured post-mortem. Intra-BLA administration of PPARα or PPARγ 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 PPARα and PPARγ antagonists increased levels of dopamine in the BLA compared with the vehicle-treated counterparts. In conclusion, PPARα and PPARγ in the BLA play a role in the expression or extinction of conditioned fear in the presence or absence of nociceptive tone.
Keywords:PPAR  fear conditioning  fear-conditioned analgesia  nociception  basolateral amygdala  GW6471  GSK0660  GW9662
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