Pretreatment with a monoclonal CGRP antibody prevents light aversion induced by peripheral CGRP in CD1 mice. A, Time spent in the light zone during sequential exposures in the light/dark chamber at 2.7 × 104 lux (left). Mice were preexposed to the chamber twice (Pre1, Pre2) at 3 d intervals to reduce exploratory drive before the first treatment (Tx1) with an intraperitoneal injection of vehicle (n = 11) or CGRP (0.1 mg/kg, two random cohorts: CGRP(1) n = 14, CGRP(2) n = 14). CGRP-treated mice spent less time in light compared with vehicle (for CGRP(1) *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; CGRP(2) #p < 0.05, ###p < 0.001, ####p < 0.0001) and compared with Pre2 and Post indicated by brackets, ***p < 0.001, ###p < 0.001, ####p < 0.0001. Four days after posttreatment, antibody treatment (Ab Tx) was done by intraperitoneal injection of control antibody (Con Ab) or CGRP-blocking antibody (CGRP Ab). The following day, mice were injected with intraperitoneal vehicle or CGRP (0.1 mg/kg). Mice that received CGRP after Con Ab (CGRP(2) +Con Ab, n = 14) spent less time in the light compared with CGRP after CGRP Ab (CGRP (1)+CGRP Ab, n = 14), *p < 0.05, **p < 0.01 and compared with vehicle after CGRP antibody (Veh+CGRP Ab, n = 11), #p < 0.05. Data are from two independent experiments. B, The mean time (±SEM) in light per 5 min interval for individual mice during the first treatment (Tx1) and second treatment (Ab Tx) after injection of Con Ab or CGRP Ab is shown. Data are from A, **p < 0.01, ##p < 0.01, ns = not significant. C, Resting time was measured concurrently with light aversion for the same mice in A and B. CGRP-treated mice and CGRP(2)+Con Ab mice spent more time (mean ± SEM) resting in the dark during Tx1 and Ab Tx, respectively (CGRP(1) *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; CGRP(2) #p < 0.05, ####p < 0.0001). D, Number of vertical beam breaks per minutes in light and dark zones. CGRP-treated mice and CGRP+Con Ab had significantly less vertical beam breaks in the dark during Tx1 (CGRP(1) **p < 0.01, ***p < 0.001; CGRP(2) #p < 0.05, ##p < 0.01, ####p < 0.0001) and Ab Tx compared with Veh+CGRP (*p < 0.05) and compared with CGRP(1)+CGRP Ab (#p < 0.05). Data are from two independent experiments.