Figure 2.
Time course of seizures, changes in muscle tone, and anxiety in mice subjected to chronic treatment with alprazolam or vehicle on withdrawal. Circles represent mean ± SEM number of seizures per animal recorded in groups of 4 vehicle- and 9 alprazolam-treated mice (A), mean ± SEM EMG activity in μV/s recorded in groups of 10 vehicle- and 10 alprazolam-treated mice (B), and mean ± SEM anxiety expressed as margin time/center time ratio from groups of 10 vehicle- and 13 alprazolam-treated mice (C), withdrawn from vehicle (○), or alprazolam (•). Multivariate ANOVA on the treatments in EMG, using the 16 measurement days as variables, showed a significant difference in the overall effect (FEMG(16,2) = 13313.54, P < 0.001), and two-way ANOVA with factors for treatment, time, and their interaction on anxiety expressed as margin time/center time ratio (Mtime/Ctime) demonstrated significant effect of treatment (FMtime/Ctime(1,276) = 256.89, P < 0.001), revealing that chronic treatment with alprazolam resulted in seizures, muscle rigidity, and anxiety on withdrawal. A total of 320 recordings performed in 20 mice were used for the analysis of the EMG, while 308 recordings from 368 mice were employed for the analysis of anxiety.