Figure 4. Effects of twice-weekly SNC80 on control and acid-depressed ICSS.

SNC80 was administered twice each week, once before lactic acid vehicle (SNC80-Veh) and once before 1.8% lactic acid (SNC80-LA), with at least 3 days between SNC80 doses. Under these conditions, SNC80 had no effect on control ICSS, but dose-dependently blocked acid-induced depression of ICSS. (a and b) Abscissae: Frequency of electrical brain stimulation in Hz (log scale). Ordinates: Percent maximum control response rate (%MCR). In this group of 6 rats, the mean±SEM MCR was 48.0±5.0. The left panel (a) shows data for SNC80 administered as a pretreatment to lactic acid vehicle. Two-way ANOVA revealed a significant main effect of frequency [F(9,45)=58.8, p<0.001] but not of SNC80 dose [F(3,15)=0.4, p=0.74], and the interaction was also not significant [F(27,135)=0.6, p=0.96]. The center panel (b) shows data for SNC80 administered as a pretreatment to 1.8% lactic acid. Two-way ANOVA revealed main effects of frequency [F(9,45)=122.8, p<0.001] and SNC80 dose [F(3,15)=5.5, p=0.009], and a significant interaction [F(27,135)=1.6, p=0.044]. Filled symbols indicate a significant difference from Veh-LA (Holm-Sidak post hoc test, p<0.05). (c) The right panel shows SNC80 effects on the total number of stimulations per component. In this group of 6 rats, the mean±SEM baseline number of stimulations/component was 221±39.2. Abscissa: Dose SNC80 in mg/kg. Ordinate: Percent baseline number of stimulations per component. Two-way ANOVA indicated a significant main effect of acid treatment [F(1,5)=11.8, p=0.019], no significant main effect of SNC80 dose [F(3,15)=1.9, p=0.18, and a significant interaction [F(3,15)=3.3, p=0.048]. The dollar sign ($) indicates a significant effect of acid treatment at a given dose of SNC80, and the asterisk (*) indicates a significant effect of SNC80 dose on acid-induced depression of ICSS (Holm-Sidak post hoc test, p<0.05). All points and bars show mean±SEM.