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

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

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 (0.3mg/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 (US)
Pages (from-to)83-91
Number of pages9
JournalJournal of Psychopharmacology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • Akt (protein kinase B)
  • endocannabinoids
  • fatty acid amide hydrolase (FAAH)
  • fear
  • pain
  • periaqueductal grey (PAG)
  • rats

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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