Fig. 1: Specific activation of D1-MSNs in the dorsal striatum together with stress exposure induces repetitive behavior.

a Schematic of the experiment. Animals were randomly assigned to either a saline or CNO (10 mg/kg) group and underwent behavioral tests without PRST exposure first. The same tests were repeated 1 week later after overnight exposure to PRST. (EYFPSaline, n = 11; EYFPCNO, n = 10; hM3DqSaline, n = 12; hM3DqCNO, n = 11). b Time spent in open arms in the EPM. Kruskal–Wallis test with post hoc Dunn’s multiple comparisons test (EYFP) (H = 18.59, P = 0.0003) and two-way ANOVA with post hoc Tukey’s test (hM3Dq) (Interactiondrug × PRST: F1, 42 = 2.141, P = 0.1509, PRST effect: F1, 42 = 30.71, P = 1.807e−06) were used for data analyses. c Total distance traveled in the EPM. A two-way ANOVA with post hoc Tukey’s test showed a significant interaction between drug (CNO) effect and stress (PRST) (F1, 42 = 13.88, P = 0.0006) in the hM3Dq-injected group. d Cumulative probability plot of the locomotor speed (Kolmogorov–Smirnov test; Saline_PRST vs CNO_PRST, P = 1.033e−10; CNO_naive vs CNO_PRST, P = 3.374e−05). e Repetitive traveling pattern in PRST-exposed mice with D1-MSN activation. Left, representative movement tracks on EPM (closed arms are indicated by darker outlines). Right, quantification (Kruskal–Wallis test with post hoc Dunn’s multiple comparisons test: H = 27.56, P = 4.499e−06). f Animals subjected to EPM and exposed to PRST once were examined in the forced swim test (FST) 5–7 days after EPM test. Each of four groups of animals (EYFPSaline, EYFPCNO, hM3DqSaline, hM3DqCNO) were divided into two groups, Naive and PRST (EYFPSaline_naive, n = 8; EYFPCNO_naive, n = 5; EYFPSaline_PRST, n = 3; EYFPCNO_PRST, n = 3; hM3DqSaline_naive, n = 5; hM3DqCNO_naive, n = 7; hM3DqSaline_PRST, n = 6; hM3DqCNO_PRST, n = 6). Kruskal–Wallis test with post hoc Dunn’s multiple comparisons test: H = 17.76, P = 0.0005.