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. Author manuscript; available in PMC: 2020 Mar 23.
Published in final edited form as: J Physiol. 2019 May 20;597(16):4293–4307. doi: 10.1113/JP277651

Figure 7: AZD7325 treatment attenuates hyperthermia-induced seizures in F1.Scn1a+/− mice with no sedative effect.

Figure 7:

(a) Cumulative generalized tonic-clonic seizure (GTCS) incidence curve for F1.Scn1a+/− mice treated with AZD7325 (AZD) or vehicle (Veh) and then subjected to hyperthermia-induced seizure threshold testing. All three doses, 10, 17.8 and 31.6 mg/kg significantly shifted the temperature threshold curve for hyperthermia-induced seizures (p < 0.0001). Vehicle treated F1.Scn1a+/− mice had median GTCS temperature threshold of 42.2°C, compared to median thresholds in the treatment groups of 42.8°C for 10 mg/kg, 43.3°C for 17.8 mg/kg, and 43.4°C for 31.6 mg/kg. P-values were determined by LogRank Mantel-Cox with n = 12 – 14 per treatment group. (b) Representative trajectory maps of the open field test in vehicle (Veh) or AZD7325 (AZD) administered mice. (c) Collective data for the time course of the distance travelled by vehicle (Veh) or AZD7325 (AZD) administered mice in the open field. Both groups show a time dependent decrease in the distance reflecting habituation to the new environment (two-way ANOVA : F(11,121) = 22.95, p < 0.0001, 5 min bins, n = 6 and 7 mice for vehicle and AZD7325 treated groups, respectively), but there is no difference between the treatment groups (two-way ANOVA : F(1,11) = 0.0030, p = 0.96, n = 6 and 7 mice for vehicle and AZD7325 treated groups, respectively). (d) Grouped data of effect of AZD on total distance travelled. AZD7325 treatment did not have an effect on total distance travelled. Mann-Whitney U test: Total distance: 36.3 ± 6.0 m (Veh) and 36.8 ± 6.2 m (AZD), p = 1.0, n = 6 and 7 mice for vehicle and AZD7325 treated groups. n.s. denotes p ≥ 0.05. (e and f) The time mice spent in the center (e) and the number of the times mice crossed into the center of the open field chamber (f) Mann-Whitney U test: Center time: 230 ± 68 s (Veh) and 295 ± 148 s (AZD), p = 0.73 (e) Center enter number: 210 ± 50 times (Veh) and 202 ± 64 s (AZD), p = 0.76 (f) n = 6 and 7 mice for vehicle and AZD7325 treated groups. n.s. denotes p ≥ 0.05.