Figure 1.
Spontaneous nicotine withdrawal measured after 7 days of nicotine exposure (5.2 mg/rat/day).
Rats previously exposed to nicotine showed (A) increased occurrence of overall withdrawal signs compared to non-exposed controls. Overall withdrawal signs were obtained for each animal by accumulating the number of events belonging to different categories of somatic withdrawal manifestations (wet dog shakes/tremors, gasp/writhes, chattering/chews) scored at 16 hours from nicotine discontinuation. Nicotine exposed rats also showed: (B) decreased distance (cm) traveled in the open field at the 16-hour time point; (C) reduced percentage (%) in open arms time measured at 34 hours from nicotine patch removal, and (D) rapid body weight gain (g). Values represent the mean (±SEM) of N = 6 subjects per group. In A, B and C, *p<0.05, **p<0.01 difference vs. control. In D, **p<0.01, ***p<0.001 difference vs. nicotine group at T = 0 h.
Table 1.
Levels of the endocannabinoids anandamide (AEA, pmol/g) in different brain structures during acute (16 h) and protracted (34 h) nicotine withdrawal phases.
Table 2.
Levels of 2-arachydonyl-sn-glycerole (2-AG, pmol/mg).
Figure 2.
Spontaneous nicotine withdrawal measured 16 hours after nicotine patches (5.2 mg/rat/day) removal was not prevented by administration of URB597 (0.0, 0.1 and 0.3 mg/kg, i.p.).
(A) overall withdrawal symptoms, (B) wet dog shakes/tremors, (C) chattering/chews, (D) gasp/writhes, (E) yawns. Values represent the mean (±SEM) of N = 8 subjects per group. #p<0.05, ##p<0.01, difference vs. “C+0.0” group.
Figure 3.
URB597 blocked nicotine withdrawal-induced anxiety-like behavior, as assessed in the elevated plus-maze and in the shock-probe defensive burying tests 34 hours after nicotine discontinuation.
(A) Animals previously exposed to nicotine (N+0.0) showed significant reduction in percent (%) open arm time compared to controls (C+0.0). URB597 returned % open arms time to control levels. Values represent the mean (±SEM) of N = 10–11 subjects per group. (B) Animals previously exposed to nicotine (N+0.0) showed significant increase in burying time (seconds) compared to controls (C+0.0). URB597 dose-dependently returned burying time to control levels. Values represent the mean (±SEM) of N = 7–8 subjects per group; *p<0.05, **p<0.01 compared to nicotine exposed receiving vehicle; #p<0.05, difference from non-nicotine exposed controls.