Fear-induced suppression of nociceptive behaviour and activation of Akt signalling in the rat periaqueductal grey: role of fatty acid amide hydrolase

Gemma K Ford, Ryan K Butler, Michelle Hogan, Michelle Roche, Karen M Doyle, John P Kelly, David A Kendall, Victoria Chapman, David P Finn

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)


The endocannabinoid system regulates nociception and aversion and mediates fear-conditioned analgesia (FCA). We investigated the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which inhibits the catabolism of the endocannabinoid anandamide and related N-acylethanolamines, on expression of FCA and fear and pain related behaviour per se in rats. We also examined associated alterations in the expression of the signal transduction molecule phospho-Akt in the periaqueductal grey (PAG) by immunoblotting. FCA was modelled by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. URB597 (0.3 mg/kg, i.p.) enhanced FCA and increased fear-related behaviour in formalin-treated rats. Conditioned fear per se in non-formalin-treated rats was associated with increased expression of phospho-Akt in the PAG. URB597 reduced the expression of fear-related behaviour in the early part of the trial, an effect that was accompanied by attenuation of the fear-induced increase in phospho-Akt expression in the PAG. Intra-plantar injection of formalin also reduced the fear-induced increase in phospho-Akt expression. These data provide evidence for a role of FAAH in FCA, fear responding in the presence or absence of nociceptive tone, and fear-evoked increases in PAG phospho-Akt expression. In addition, the results suggest that fear-evoked activation of Akt signalling in the PAG is abolished in the presence of nociceptive tone.
Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalJournal of Psychopharmacology
Issue number1
Publication statusPublished - Jan 2012


  • Amidohydrolases
  • Analgesia
  • Animals
  • Arachidonic Acids
  • Behavior, Animal
  • Benzamides
  • Cannabinoid Receptor Modulators
  • Carbamates
  • Conditioning (Psychology)
  • Endocannabinoids
  • Ethanolamines
  • Exploratory Behavior
  • Fear
  • Formaldehyde
  • Hippocampus
  • Male
  • Motor Activity
  • Nociception
  • Pain
  • Periaqueductal Gray
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Signal Transduction


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