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. Author manuscript; available in PMC: 2011 Mar 1.
Published in final edited form as: Nat Neurosci. 2010 Aug 22;13(9):1113–1119. doi: 10.1038/nn.2616

Figure 2. Prolonged blockade of MAGL and FAAH causes differential analgesic tolerance.

Figure 2

(a) Acute treatment with JZL184 caused elevated withdrawal latencies in the tail immersion test for thermal nociception, while this hypoalgesic response was not observed following chronic treatment with JZL184 (p = 0.33). A similar magnitude hypoalgesic effect was observed in mice treated acutely with PF-3845, and this effect was maintained following chronic treatment with PF-3845. (b, c) Acute treatment with JZL184 or PF-3845 reduced mechanical (b) and cold (c) allodynia in nerve-injured mice. The anti-allodynic effects of PF-3845, but not JZL184, were maintained following chronic administration. (d) MAGL+/+, MAGL+/−, and MAGL−/− mice display similar tail withdrawal latencies. (e, f) Chronic JZL184 treatment causes cross-tolerance to the anti-allodynic effects of WIN55,212-2 and PF-3845. Data are presented as means ± s.e.m., with n = 6–8 per group in all studies. *p < 0.05, **p < 0.01, ***p < 0.001 versus vehicle-treated or wild-type littermate control mice (Dunnett’s post-hoc test). ##p < 0.01, ###p < 0.001 versus respective acute drug treatment group (Bonferroni test).