Extended Data Fig. 7: Dopamine receptor manipulation changes threat avoidance.
From: Dopamine in the tail of the striatum facilitates avoidance in threat–reward conflicts
(a-c) Mice with ablation of TS-projecting dopamine neurons were injected with D1 (b) or D2 (c) receptor agonists in TS for rescue experiments. Control mice received vehicle injection during surgery and test days. Cannula tip positions are plotted on the nearest reference slice (a) (Paxinos and Franklin, 2019). Reactive avoidance increased from the first trial after D1 agonist injection (mean ± SEM) (p = 1.0 × 10−3, 0 µg vs. 5 µg, c2 = 12, chi-squared test, n = 6 animals for each), and then gradually decreased (p = 2.1 × 10−3, 5 µg, p = 0.08, 0.5 µg, p = 0.77, 0 µg, regression coefficient of the avoidance rate with trials, two-sided t-test, n = 6 animals for each). Mean ± SEM. Reactive avoidance increased from the first trial after D2 receptor agonist injection (p = 1.0 × 10−3, 0 µg vs 2 µg, c2 = 12, chi-squared test, n = 6 animals for each), and gradually changed across time depending on the agonist doses (p = 5.1 × 10−3, F(2,30) = 6.50, session × dose interaction, 2-way repeated measures ANOVA, n = 6 animals each). Dopamine ablation mice with intermediate level (0.2 µg) of D2 receptor agonist gradually decreased reactive avoidance (p = 0.43, 2 µg, p = 0.042, 0.2 µg, p = 0.44, 0 µg, regression coefficient of the avoidance rate with trials, two-sided t-test, n = 6 animals each). Mean ± SEM. (d) Avoidance decreased with D2 receptor antagonist injection in monster Day 1 (avoidance rate, p = 0.014; predictive avoidance, p = 0.21; reactive avoidance, p = 0.017, two-sided t-test compared to control animals with vehicle injection, n = 6 animals for each). (e) Avoidance increased when D2 receptor agonists were injected before Day 2-3 after animals experienced monster session Day 1 (avoidance rate, p = 0.022; predictive avoidance, p = 0.16; reactive avoidance, p = 0.043, two-sided t-test compared to control animals with vehicle injection, n = 6 animals for each). *P < 0.05.
