Fear-induced suppression of nociceptive behaviour and activation of Akt signalling 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.

• Authors: Ryan K Butler, Gemma K Ford, Michelle Hogan, Michelle Roche, Karen M Doyle, John P Kelly, David A Kendall, Victoria Chapman, David P Finn
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 26 Issue 1 Pg. 83-91 (Jan 2012) ISSN: 1461-7285 [Electronic] United States
• PMID: 21926424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Benzamides
• Cannabinoid Receptor Modulators
• Carbamates
• Endocannabinoids
• Ethanolamines
• N-acylethanolamines
• Polyunsaturated Alkamides
• cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
• Formaldehyde
• Proto-Oncogene Proteins c-akt
• Amidohydrolases
• fatty-acid amide hydrolase
• anandamide

Topics

• Amidohydrolases (antagonists & inhibitors, metabolism)
• Analgesia (methods)
• Animals
• Arachidonic Acids (metabolism)
• Behavior, Animal (drug effects, physiology)
• Benzamides (pharmacology)
• Cannabinoid Receptor Modulators (metabolism)
• Carbamates (pharmacology)
• Conditioning, Psychological (drug effects, physiology)
• Endocannabinoids
• Ethanolamines (metabolism)
• Exploratory Behavior (drug effects, physiology)
• Fear (drug effects, physiology)
• Formaldehyde (pharmacology)
• Hippocampus (drug effects, metabolism, physiology)
• Male
• Motor Activity (drug effects, physiology)
• Nociception (drug effects, physiology)
• Pain (metabolism, physiopathology)
• Periaqueductal Gray (drug effects, enzymology, metabolism, physiology)
• Polyunsaturated Alkamides (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Signal Transduction (drug effects, physiology)