Figure 9.

mPFC dopaminergic response counteracts induction of social avoidance by social defeat. A, Negative correlation between dopamine turnover in mPFC and social avoidance after repeated social defeat. After repeated social defeat for 10 days, the level of social avoidance was measured. Mice then underwent an additional defeat on the next day and were sacrificed for the measurement of dopamine turnover. Dopamine turnover was normalized to the mean value in control mice run at the same time. Each dot represents the data point of an individual mouse. There is a significant negative correlation (solid line) between the level of social avoidance and dopamine turnover (R² = 0.291, p < 0.05, Pearson's test). B, Assessment of stereotaxic coordinates for drug injection to mPFC. Ibotenic acid solution with fluorescent microspheres was injected in a group of mice separate from those in C and D to make neurotoxic lesions to assess drug diffusion in mPFC. The stereotaxic coordinate for drug injection was centered at the infralimbic cortex. Note that neurotoxic lesions (left) and fluorescent microspheres (right) are mainly located in the infralimbic cortex, although extending to the prelimbic cortex. C, Selective depletion of mPFC dopamine content. Saline or 6-hydroxydopamine (6OHDA) was injected into mPFC with systemic injection of desipramine and citalopram, and at 7–10 d after surgery the contents of dopamine (DA), noradrenaline (NA), and serotonin (5HT) in mPFC and that of DA in NAc were measured. Circular regions in mPFC and NAc shown in Figure 7A were taken for this measurement. Values were normalized to those in respective saline controls. The number of mice is shown below each bar; **p < 0.01 for unpaired t test. D, Induction of social avoidance after the first exposure to social defeat in mice with mPFC dopaminergic lesion. Mice were injected with 6OHDA or saline into mPFC and, after postoperative recovery for 7–10 d, these mice were subjected to repeated social defeat. The level of social avoidance is shown before social defeat (Day 0) and about 18 h after the first (Day 1), fourth (Day 4), and tenth (Day 10) social defeat; n = 9 for sham-operated mice and n = 8 for dopaminergic lesioned mice; *p < 0.05 for post hoc Bonferroni's test after two-way ANOVA.