Fig. 1. Sodium valproate. Total distance travelled over the 30 min test period is shown as the mean ± S.E.M. in centimetres (n = 9–12 mice). (a) Administration of D-amphetamine (1.25 mg/kg i.p.) plus chlordiazepoxide (6.25 mg/kg i.p.) produced a significant increase in total distance travelled; ^##p < 0.01 vs. the vehicle group. Pre-treatment (60 min) with sodium valproate (75–300 mg/kg p.o.) reduced total distance travelled; ^*p < 0.05, ^**p < 0.01 vs. the D-amphetamine/chlordiazepoxide group. (b) Administration of D-amphetamine (1.25 mg/kg i.p.) produced a significant increase in total distance travelled. Pre-treatment (60 min) with sodium valproate (75–300 mg/kg p.o.) had no effect on the hyperactivity, which remained significantly elevated; ^#p < 0.05, ^##p < 0.01 vs. the vehicle group. (c) Administration of valproate (75 or 300 mg/kg p.o.) alone had no effect on total distance travelled. A small, but significant decrease in total distance travelled was observed with 150 mg/kg p.o. valproate.

Fig. 2. Carbamazepine. Total distance travelled over the 30 min test period is shown as the mean ± S.E.M. in centimetres (n = 9–12 mice). (a) Administration of D-amphetamine (1.25 mg/kg i.p.) plus chlordiazepoxide (6.25 mg/kg i.p.) produced a significant increase in total distance travelled; ^##p < 0.01 vs. the vehicle group. Pre-treatment (60 min) with carbamazepine (10–40 mg/kg p.o.) reduced the total distance travelled; ^**p < 0.01 vs. the D-amphetamine/chlordiazepoxide group. (b) Administration of D-amphetamine (1.25 mg/kg i.p.) produced a significant increase in total distance travelled; ^#p < 0.05 vs. the vehicle group. Pre-treatment (60 min) with carbamazepine (10–20 mg/kg p.o.) had no effect on the total distance travelled, which remained significantly elevated. Carbamazepine (40 mg/kg p.o.) significantly reduced the total distance travelled; ^**p < 0.01 vs. the D-amphetamine group. (c) Carbamazepine (10–20 mg/kg p.o.) alone had no significant effect on total distance travelled, but 40 mg/kg p.o. significantly reduced total distance travelled; ^**p < 0.01 vs. the vehicle group.

Fig. 3. Lamotrigine. Total distance travelled over the 30 min test period is shown as the mean ± S.E.M. in centimetres (n = 9–12 mice). (a) Administration of D-amphetamine (1.25 mg/kg i.p.) plus chlordiazepoxide (6.25 mg/kg i.p.) produced a significant increase in total distance travelled; ^#p < 0.05 vs. the vehicle group. Pre-treatment (120 min) with lamotrigine (5–20 mg/kg p.o.) produced a dose-dependent reduction in the total distance travelled, which was significant at 20 mg/kg; ^**p < 0.01 vs. the D-amphetamine/chlordiazepoxide group. In this experiment, pre-treatment (60 min) with valproate (150 mg/kg p.o.) also significantly reduced the hyperactivity. (b) Administration of D-amphetamine (1.25 mg/kg i.p.) produced a significant increase in total distance travelled; ^##p < 0.01 vs. the vehicle group. Pre-treatment (120 min) with lamotrigine (5–20 mg/kg p.o.) reduced the total distance travelled in a dose-dependent manner, such that at the higher doses, it was no longer significantly elevated with respect to the D-amphetamine group. (c) Lamotrigine (5–20 mg/kg p.o.) alone had no significant effect on total distance travelled.

Fig. 4. Chlordiazepoxide alone. Total distance travelled over the 30 min test period is shown as the mean ± S.E.M. in centimetres (n = 10–11). Chlordiazepoxide alone produced a small, but insignificant increase in total distance travelled. Lamotrigine (20 mg/kg p.o.) did not alter the effect of chlordiazepoxide. Valproate (150 mg/kg p.o.) and carbamazepine (20 mg/kg p.o.) both reduced total distance travelled in the presence of chlordiazepoxide; ^*p < 0.05, ^**p < 0.01 vs. the chlordiazepoxide group.

Fig. 5. In each of three separate experiments, infusion of pentylenetetrazole (0.5 mg/min) into the tail vein produced a myoclonic seizure (first twitch) followed by a tonic-clonic seizure. Group size was 5–7 mice. (a) Sodium valproate (75–300 mg/kg p.o., 60 min pre-treatment time) dose-dependently increased the amount of pentylenetetrazole required to induce a first twitch and a tonic-clonic seizure. The lowest dose that produced a significant effect on either seizure was 300 mg/kg (^**p < 0.01, ^***p < 0.001 vs. the vehicle treated group). (b) Carbamazepine (10–40 mg/kg p.o., 60 min pre-treatment time) dose-dependently increased the amount of pentylenetetrazole required to induced a tonic-clonic seizure, but had no effect on the first twitch. The lowest dose that produced a significant effect on the tonic-clonic seizure was 20 mg/kg (^**p < 0.01 vs. the vehicle treated group). (c) Lamotrigine (5–20 mg/kg p.o., 240 min pre-treatment time) dose-dependently increased the amount of pentylenetetrazole required to induced a first twitch and a tonic-clonic seizure. The lowest dose that produced a significant effect on either seizure type was 20 mg/kg (^*p < 0.05, ^**p < 0.01 vs. the vehicle group).