Anxiety-like symptoms induction and decrease exploratory activity after unpredictable sound stress
The open field test was evaluated in 1st, 7th, and 14th-day post-stress induction or in NST group. In this apparatus it was measured grooming (s), rearing (s), sniffing (s), time into the peripheral zone, and number of crossings. The ST group spent more time grooming compared with the NST group, on both the 1st and the 7th post-stress, but not on the 14th day (Fig. 3A). On day 7, the ST females spent more time in grooming behavior compared to male ST mice (Fig. 3A). Regarding sniffing time, in the ST group it was significantly less both in 1 and 7 days (Fig. 3B). At day 7th after stress induction female mice had a higher reduction in the sniffing time compared to male ST mice (Fig. 3B). For the time of rearing male and female ST mice spent less time in this behavior at day 7th after stress when compared to NST group (Fig. 3C). Also, female ST mice showed a difference when compared to male ST mice presenting a lower time for rearing at day 7th post stress (Fig. 3C). When assessing the number of crossings, we perceived a reduction in this behavior on the 7th day only in ST female compared to NST female group and ST male mice (Fig. 3D and 3E). Also, we demonstrated that ST mice stayed longer in the peripheral zone compared to the NST group at the 7th-day post-stress induction, but not on days 1 and 14 (Fig. 3F and 3G). Also, when comparing the sex effect in the ST group, we evidenced that ST females spent more time in the peripheral zone compared to ST males at day 7th after stress (Fig. 3F and 3G). No significant difference was seen between groups in locomotor activity assessed by distance traveled (data not shown). Thus, the anxiety-like symptoms induction and decrease exploratory activity was mainly detected at 7th-day post-stress induction. Therefore, this day after stress induction was chosen to measure the antinociceptive effect of CGRP antagonist treatment and the other analysis (plasmatic levels of pro-inflammatory cytokines and CGRP, and the mRNA level of some migraine-related markers in the trigeminal ganglion).