SNC80 was administered for 3 consecutive days. On Days 1 and 3, rats received 10 mg/kg SNC80 followed by lactic acid vehicle (10 SNC80-Veh), whereas on Day 2, rats received 10 mg/kg SNC80 followed by 1.8% lactic acid (10 SNC80-LA). These results were compared to effects of SNC80 vehicle + lactic acid vehicle (Veh-Veh) and SNC80 vehicle + 1.8% lactic acid (Veh-LA). Top panels (a and b) compare effects of Veh-Veh treatment with Day 1 and Day 3 10 SNC80-Veh treatment. SNC80 decreased ICSS on Day 1 but not on Day 3. (a) Abscissa: frequency of electrical brain stimulation in Hz (log scale). Ordinate: Percent maximum control rate (%MCR). For this group of 9 rats, the mean±SEM MCR was 60.3±2.5. Two-way ANOVA revealed a significant main effect of frequency [F(9,72)=70.0, p<0.001], no effect of treatment [F(2,16)=1.8, p=0.20] and a significant interaction [F(18,144)=3.2, p<0.001], and filled symbols indicate a significant difference from Veh-Veh (Holm-Sidak post hoc test, p<0.05). (b) Abscissa: Treatment conditions. Ordinate: Percent baseline number of stimulations per component. For this group of 9 rats, the mean±SEM baseline number of stimulations per component was 281.8±25.7. One-way ANOVA indicated a significant effect of treatment [F(2,16)=4.7, p=0.025). The dollar sign ($) indicates significantly different from Veh-Veh, and the asterisk (*) indicates significantly different from Day 1 10 SNC80-Veh (Newman-Keuls, p<0.05). The bottom panels (c and d) compare effects of Veh-Veh, Veh-LA and Day 2 10 SNC80-LA. Under these conditions, SNC80 completely blocked acid-induced depression of ICSS on Day 2. (c) Abscissa and ordinate as in (a). Two-way ANOVA revealed main effects of frequency [F(9,72)=77.9, p<0.001] and treatment [F(2,16)=12.7, p<0.001] and a significant interaction [F(18,144)=3.8, p<0.001], and filled symbols indicate a significant difference from Veh-LA (Holm-Sidak post hoc test, p<0.05). (d) Abscissa and ordinate as in (b). One-way ANOVA indicated a significant effect of treatment [F(2,16)=10.0, p=0.002). The dollar sign ($) indicates significantly different from Veh-Veh, and the asterisk (*) indicates significantly different from Veh-LA (Newman-Keuls, p<0.05). All points and bars show mean±SEM.