Figure 4.
5-HT1A antagonism partially prevented antinociception and completely blocked the anxiolytic properties of repeated CBD administration in SNI rats. (A) Scheme illustrating the timing of SNI induction, behavioral and electrophysiological experiments. (B) Mechanical hypersensitivity was measured with von Frey filaments at day 15 (D0), 19 (D5), and 23 (D7) after SNI surgery. Spared nerve injury rats treated with veh (n = 9), CBD alone (5 mg/kg/day, subcutaneously [s.c.], for 7 days, n = 9), or in combination with WAY (2 mg/kg/day, s.c., for 7 days, 10 minutes before CBD, n = 8) and WAY alone (2 mg/kg/day, s.c., for 7 days, n = 7) were tested. Each point of the line represents mean ± SEM expressed as mean of 50% paw withdrawal threshold (g). Two-way ANOVA for repeated measures followed by Bonferroni post hoc comparisons. ***P < 0.001 vs SNI/veh; ##P < 0.01 vs SNI/WAY + CBD at D7. (C) Horizontal movement traces in the OFT of SNI rats treated with veh, CBD alone (5 mg/kg/day, s.c., for 7 days), or in combination with CPZ (10 mg/kg/day, s.c., for 7 days, 10 minutes before CBD) and WAY alone (2 mg/kg/day, s.c., for 7 days). (D-F) Distance travelled (cm) (D), time spent (s) in the central area (E), and number of entries in the central area (F) of the OFT. Spared nerve injury rats treated with veh (n = 9), CBD alone (5 mg/kg/day, s.c., for 7 days, n = 9), or in combination with WAY (2 mg/kg/day, s.c., for 7 days, 10 minutes before CBD, n = 8) and WAY alone (2 mg/kg, s.c., for 7 days, n = 7) were tested. Each bar represents mean ± SEM. In D-F, each point represents data from an individual rat. One-way ANOVA followed by Bonferroni post hoc comparisons. **P < 0.01 vs SNI/veh; #P < 0.05; and ##P < 0.01 vs SNI/CBD. (G) Percentage of time (%) spent in the open arms in the EPMT. Each bar represents mean ± SEM. (H) Horizontal movement traces in the EPMT of SNI rats treated with veh (n = 9), CBD alone (5 mg/kg/day, s.c., for 7 days, n = 9), or in combination with WAY (2 mg/kg/day, s.c., for 7 days, 10 minutes before CBD, n = 8) and WAY alone (2 mg/kg/day, s.c., n = 7) were tested. (I and J) Latency to feed (s) in the novel (I) and familiar (J) environments in the NSFT. Each symbol represents mean ± SEM. In G, each point represents data from an individual rat. One-way ANOVA followed by Bonferroni post hoc comparisons. **P < 0.01 vs SNI/veh; #P < 0.05 vs SNI/CBD. ANOVA, analysis of variance; CBD, cannabidiol; CPZ, capsazepine; EPMT, elevated plus maze test; N.S., not significant; NSFT, novelty-suppressed feeding test; OFT, open-field test; SNI, spared nerve injury.