Figure 1.

Single dose of ganaxolone (GAN, 30 mg/kg) increased the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate (NMDA) receptor current ratio and the rectification index in ventral tegmental area (VTA) dopamine (DA) neurons of midbrain slices obtained ex vivo 1–6 days after the drug administration. (a) Locomotor activity after acute injection of GAN (10 mg/kg, n=17; and 30 mg/kg, n=24) and vehicle control (n=30) in 3–4-week-old Th-EGFP mice. The data are given as the mean distance travelled for 15-min periods preceding the time points (SEM values are within the symbols). (b) Cumulative locomotor activity (mean+SEM) for 60 min after injection for the mice is shown in a. *P<0.05 for significance of difference from the vehicle group. (c) Examples of AMPA and NMDA receptor-mediated current traces for vehicle- and GAN (30 mg/kg)-treated young transgenic Th-EGFP mice observed 24 h after the injection. (d) Time course of the effects of vehicle and GAN (10 and 30 mg/kg) administration on AMPA/NMDA ratios of VTA DA neurons is shown as mean bars+SEM (n=7–11 mice), the effect by the higher GAN dose persisting at least 6 days after the injection. (e) Representative AMPA receptor-mediated current traces in the VTA DA neurons recorded at −70 and +40 mV 24 h after vehicle and GAN (30 mg/kg) administrations in Th-EGFP mice, in the presence of spermine in the recording pipette solution. Decreased currents at +40 mV after GAN suggest increased rectification because of insertion of new GluA2-lacking AMPA receptors. (f) Time course of the effects of vehicle and GAN (10 and 30 mg/kg) administration on the rectification index (response at −70 mV/response at +40 mV) of VTA DA neurons is shown as mean bars+SEM (n=9–11 mice), indicating persistence of the effect for at least 6 days. *P<0.05, **P<0.01, ***P<0.001 (ANOVA with Bonferroni test or Student's t-test).