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Gaspar JC;Okine BN;Llorente-Berzal A;Roche M;Finn DP;
Molecules (Basel, Switzerland)
Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone.
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Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPAR┐, PPAR▀/┐, PPAR┐) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPAR┐ (GW6471), PPAR▀/┐ (GSK0660) or PPAR┐ (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPAR┐ and PPAR▀/┐ antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPAR┐ antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPAR┐ and PPAR▀/┐ in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPAR┐ potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone.
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