Fear-induced suppression of nociceptive behaviour and activation of signal transduction molecules in the rat periaqueductal grey: role of fatty acid amide hydrolase.
Butler, Ryan K. ; Ford, Gemma K. ; Hogan, Michelle ; Roche, Michelle ; Doyle, Karen M. ; Kelly, John P. ; Finn, David P.
Butler, Ryan K.
Ford, Gemma K.
Hogan, Michelle
Roche, Michelle
Doyle, Karen M.
Kelly, John P.
Finn, David P.
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Publication Date
2011-09-17
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Article
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Citation
Butler RK, Ford GK, Hogan M, Roche M, Doyle KM, Kelly JP, Kendall DA, Chapman V, Finn DP (2011). Fear-induced suppression of nociceptive behaviour and activation of signal transduction molecules in the rat periaqueductal grey: role of fatty acid amide hydrolase.
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 (0.3 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.
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Sage
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Attribution-NonCommercial-NoDerivs 3.0 Ireland