Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the rat hypothalamus following an immunological stressor
Finn, David P.
MetadataShow full item record
This item's downloads: 382 (view details)
Kerr DM, Burke NN, Ford GK, Connor TJ, Harhen B, Egan LP, Finn DP, Roche M (2012) 'Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the rat hypothalamus following an immunological stressor'. Neuroscience, 204 :53-63.
The endocannabinoid system is an important regulator of the nervous, neuroendocrine and immune systems, thus representing a novel therapeutic target for stress-related neuroinflammatory and psychiatric disorders. However, there is a paucity of data relating to the effects of endocannabinoids on neuroinflammatory mediators following an immune stress/challenge in vivo. This study investigated the effects of URB597, a selective inhibitor of fatty acid amine hydrolyase (FAAH), the enzyme that preferentially metabolises anandamide, on lipopolysaccharide (LPS)-induced increases in the expression of immune mediators in the hypothalamus. Systemic administration of URB597 increased the levels of anandamide and the related N-acylethanolamines, N-palmitoyl ethanolamide and N-oleoyl ethanolamide, but not 2-arachidonoyl glycerol, in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in interleukin (IL)-1Beta expression while concurrently augmenting the LPS-induced increase in suppressor of cytokine signalling (SOCS)-3 expression. In addition, URB597 tended to enhance and reduce the LPS-induced increase in IL-6 and IL-10 mRNA expression respectively. LPS-induced increases in peripheral cytokine levels or plasma corticosterone were not altered by URB597. The present study provides evidence for a role for FAAH in the regulation of LPS-induced expression of inflammatory mediators in the hypothalamus. Improved understanding of endocannabinoidmediated regulation of neuroimmune function has fundamental physiological and potential therapeutic significance in the context of stress-related disorders.
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.
The following license files are associated with this item: