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Butler, RK,Ford, GK,Hogan, M,Roche, M,Doyle, KM,Kelly, JP,Kendall, DA,Chapman, V,Finn, DP
2012
January
Journal Of Psychopharmacology
Fear-induced suppression of nociceptive behaviour and activation of Akt signalling in the rat periaqueductal grey: role of fatty acid amide hydrolase
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Akt (protein kinase B) endocannabinoids fatty acid amide hydrolase (FAAH) fear pain periaqueductal grey (PAG) rats STRESS-INDUCED ANALGESIA ENDOGENOUS CANNABINOID SYSTEM ROSTRAL VENTROMEDIAL MEDULLA PROTEIN-KINASE B/AKT CONDITIONED ANALGESIA ENDOCANNABINOID SYSTEM OPIOID ANALGESIA FAAH INHIBITOR RECEPTOR MODULATION
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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.
DOI 10.1177/0269881111413823
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