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We measured the endogenous content of <jats:italic>N<\/jats:italic>\u2010arachidonoylethanolamine and 2\u2010arachidonoylglycerol and the activity of their biosynthetic enzymes (<jats:italic>N<\/jats:italic>\u2010acyl\u2010phosphatidylethanolamine\u2010hydrolyzing phospholipase\u00a0D and diacylglycerol lipase, respectively) and hydrolytic enzymes [fatty acid amide hydrolase (<jats:styled-content style=\"fixed-case\">FAAH<\/jats:styled-content>) and monoacylglycerol lipase, respectively] and of their target receptors (type\u00a01 cannabinoid receptor, type\u00a02 cannabinoid receptor, and transient receptor potential vanilloid\u20101) in the brains of wild\u2010type and R6\/2 mice of different ages, as well as in the striatum and cortex of 12\u2010week\u2010old animals. In addition, we measured <jats:styled-content style=\"fixed-case\">FAAH<\/jats:styled-content> activity in lymphocytes of R6\/2 mice. In the whole brains of 12\u2010week\u2010old R6\/2 mice, we found reductions in <jats:italic>N<\/jats:italic>\u2010acyl\u2010phosphatidylethanolamine\u2010hydrolyzing phospholipase\u00a0D activity, diacylglycerol lipase activity and cannabinoid receptor binding, mostly associated with changes in the striatum but not in the cortex, as well as an increase in 2\u2010arachidonoylglycerol content as compared with wild\u2010type littermates, without any other change in <jats:styled-content style=\"fixed-case\">ECS<\/jats:styled-content> elements. Then, our analysis was extended to <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>43 cells, an inducible cellular model of <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> derived from rat <jats:styled-content style=\"fixed-case\">ST<\/jats:styled-content>14A cells. In both induced and noninduced conditions, we demonstrated a fully functional <jats:styled-content style=\"fixed-case\">ECS<\/jats:styled-content>. Overall, our data suggest that the <jats:styled-content style=\"fixed-case\">ECS<\/jats:styled-content> is differently affected in mouse and human <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>, and that <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>43 cells are suitable for high\u2010throughput screening of <jats:styled-content style=\"fixed-case\">FAAH<\/jats:styled-content>\u2010oriented drugs affecting <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> progression.<\/jats:p>","DOI":"10.1111\/febs.12329","type":"journal-article","created":{"date-parts":[[2013,5,9]],"date-time":"2013-05-09T14:40:23Z","timestamp":1368110423000},"page":"3376-3388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["<i>In\u00a0vitro<\/i> and <i>in\u00a0vivo<\/i> models of <scp>H<\/scp>untington's disease show alterations in the endocannabinoid 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