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. 2014 Sep 3;40(2):488–501. doi: 10.1038/npp.2014.198

Figure 2.

Figure 2

Analysis of anxiety- and depression-like behavior, and hyperalgesia. (a and b) Elevated plus maze (EPM): vehicle-treated CUS mice showed reduced duration (a) and frequency (b) in the open arms of the EPM indicating an increase in anxiety-like behavior as compared with controls. URB597 administration increased duration (a) and frequency (b) of CUS mice in the open arms, indicating an anxiolytic effect. JZL184 and combo (URB597+JZL184) treatments decreased duration (a) and frequency (b) of control mice in the open arms of EPM, and had no significant effects in CUS mice. (c and d) Light–dark test LDT: vehicle-treated CUS mice showed reduced time (c) and frequency (d) in the lit compartment of the LDT as compared with controls. URB597, JZL184, and combo administration increased the time (c) and the frequency (d) of CUS mice in the lit compartment, suggesting reduced anxiety-like behavior. (e and f) Forced swim test (FST): vehicle-treated CUS mice spent more time immobile (e) and showed shortened latency to the first immobility in the forced swim test (f) as compared with controls, suggesting increased depression-like behavior. In control mice, JZL184 and combo treatments prolonged immobility time and shortened latency to the first immobility, but had no effect in CUS mice (e and f). URB597 had no effect in both animal groups (e and f). Time spent in open arms of EPM is expressed as percentage of total test time (300 s) and frequency as percentage of total arm entries. Time spent in the lit compartment of LDT and immobility time in FST are expressed as percentage of total test time (300 s). Frequency in LDT refers to the total number of entries in the lit compartment. (g) Hot plate test: CUS mice treated with vehicle showed a shorter latency of reaction to the heat source as compared with the vehicle-treated control group (g). URB597, JZL184, and combo treatment prolonged the latency of reaction in CUS mice, indicating an anti-nociceptive effect (g). (h) Von Frey's filaments test, day 0: CUS mice treated with vehicle showed decreased pain threshold and, thus, increased mechanical hyperalgesia as compared with the vehicle-treated control group. Drug treatments did not reverse the CUS-induced mechanical hyperalgesia in mice (h). Data are expressed as stimulus intensity in gram (g) that elicited the response to determine paw withdrawal threshold (h). Statistical differences between control and CUS mice are indicated above the CUS bar; differences between specific groups are shown on the indicated lines. *p<0.05, **p<0.01, ***p<0.001, Bonferroni's multiple comparison tests after significant two-way ANOVA; n=8–10 animals in each group. Additional statistical analyses are reported in Table 2.