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

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 PPAR alpha, PPAR beta/delta, and PPAR gamma 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 alpha (GW6471) PPAR beta/delta (GSK0660), or PPAR gamma (GW9662) antagonists before arena re-exposure. Pain and fear-related behaviour were assessed, and neurotransmitters/endocannabinoids measured post-mortem. Intra-BLA administration of PPAR alpha or PPAR gamma 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 alpha and PPAR gamma antagonists increased levels of dopamine in the BLA compared with the vehicle-treated counterparts. In conclusion, PPAR alpha and PPAR gamma in the BLA play a role in the expression or extinction of conditioned fear in the presence or absence of nociceptive tone.

Automated summary

There is evidence suggesting that peroxisome proliferator-activated receptors (PPARs) are involved in pain, cognition, and anxiety. However, their role in pain-fear interactions is still unclear. This study investigated the effects of PPAR antagonists on nociceptive behavior, fear-conditioned analgesia (FCA), and conditioned fear in the amygdala. The results indicate that PPAR alpha and PPAR gamma in the amygdala play a role in the expression or extinction of conditioned fear.