Fig. 4.

JZL184 raises interstitial levels of 2-AG following neuronal depolarization. Effects of JZL184 (10 mg kg^-1, i.p.) on interstitial levels of 2-AG and AEA were measured by in vivo microdialysis sampling from the nucleus accumbens of C57Bl/6 mice. Endocannabinoid release was stimulated by neuronal depolarization during perfusion with a high potassium & calcium artificial CSF solution (t = 0-90 min; shaded bar). Depolarization significantly increased dialysate 2-AG levels in both vehicle-(F(10,50) = 2.12, p < 0.05) and JZL184-treated (F(10,70) = 5.567, p < 0.0001) mice and this effect was substantially more robust in JZL184 treated animals as demonstrated by analysis of both the temporal profile (pretreatment x time interaction (F(10,120) = 3.355, *, p < 0.001; a) and area under the curve (AUC) measures (AUC t = 0-150 min; F(1,12) = 8.737; *, p < 0.05; b). There was no significant alteration in dialysate AEA levels following JZL184 administration and no significant effect of the high potassium/calcium solution on dialysate AEA levels in either group of mice as determined by analysis of both temporal profile and AUC measures (c and d). Data are the mean ± SEM of the percent change from baseline levels. Baseline dialysate 2-AG levels were 4.6 ± 0.7 nM and 4.2 ± 0.4 nM and dialysate AEA levels were 0.54 ± 0.1 nM vs. 0.58 ± 0.08 nM for the JZL184 (n = 8) and vehicle (n = 6) groups, respectively. Pretreatments with JZL184 were administered at t = -60 min (denoted by arrow).