Figure 6.
Effect of low-dose challenge. A, B, Insets, The proportion of firing rate increase or decrease responses to low-dose amphetamine (0.5 mg/kg) in preexposed rats (challenge 2) compared with drug-naive animals. In mPFC (A), previous amphetamine exposure caused a predominantly inhibitory response to the low dose of amphetamine that was opposite to the predominantly excitatory response induced by the same dose in drug naive animals (χ2 = 70.0; p < 0.001). In OFC (B), a higher proportion of neurons showed an excitatory response in preexposed rats (χ2 = 13.44; p < 0.01). The y-axis shows the percentage of neurons. A, B, The average ± SEM firing rates of neurons with sustained increase (red) or decrease (blue) responses to low-dose amphetamine in mPFC (A) and OFC (B). Low-dose challenge amplified the magnitude of inhibitory responses in mPFC and excitatory responses in OFC compared with acute low-dose treatment (two-way ANOVA with time as repeated measure; mPFC, increase responses, treatment, F(1,120) = 5.87, p < 0.05; time, F(35,4200) = 8.08, p < 0.001; treatment × time interaction, F(35,4200) = 4.33, p < 0.001; decrease responses, treatment, F(1,99) = 7.04, p < 0.01; time, F(35,3465) = 2.61, p < 0.05; treatment × time interaction, F(35,3465) = 17.97, p < 0.001; OFC, increase responses, treatment, F(1,82) = 3.68, p < 0.05; time, F(35,2870) = 13.22, p < 0.001; treatment × time interaction, F(35,2870) = 2.99, p < 0.05; decrease responses, treatment, F(1,38) = 3.84, p = 0.05; time, F(35,1330) = 3.58, p < 0.05; treatment × time interaction, F(35,1330) = 2.58, p < 0.05). Responses to acute 2 mg/kg amphetamine (day 1) is shown as a red dotted line for comparison. Time of injection is indicated as 0. Chal2, Challenge2.