Fig. 4: Chemogenetically-induced nigrostriatal hypodopaminergia leads to a prolonged negative motivational, but not affective, state.

A Behavioral screening timeline. B Quantification of hM4Di-mCherry and mCherry expression in distal (dSNc), medial SNc (mSNc) and VTA. Three-way ANOVA showed significant effect of the area [F_{(2, 140)} = 346.7, P < 0.01, η² = 0.83], but no effect of transgene, treatment or any interaction between these factors [F_s < 1.31, P > 0.27, partial η² < 0.02]. C Number of 2.5%-sucrose deliveries obtained in 60-min self-administration (SA) sessions under continuous reinforcement (FR1), during baseline (BL), “C21/NaCl” and “Wash” sessions, in hM4Di rats treated with C21 (orange, n = 8) or NaCl (red, n = 9) and mCherry rats treated with C21 (gray, n = 10) or NaCl (white, n = 10). RM three-way ANOVA showed a significant session x transgene x treatment interaction [F_{(11, 363)} = 2.67, P < 0.01, partial η² = 0.07]. D Mean sucrose deliveries obtained during “C21/NaCl” sessions normalized to baseline. Two-way ANOVA showed a significant transgene x treatment interaction [F_{(1, 33)} = 13.38, P < 0.001, partial η² = 0.29]. E—I Distance traveled over the course of a 30-min session in an open area (OA) (E), number of adjusting left and right forepaws in a stepping test (F), sucrose preference measured over a 60-min 2.5%-sucrose two-bottle-choice (2BC) drinking session (G), percentage of time spent in the light area in a light/dark avoidance test (LDA) (H) and time spent immobile in a forced swim test (FST) (I) in hM4Di rats treated with C21 (orange, n = 12) or NaCl (red, n = 11) and mCherry rats treated with C21 (gray, n = 13) or NaCl (white, n = 12). Two- or three-way ANOVA found no interaction implicating the transgene and the treatment [F_s < 1.7, P > 0.2, partial η² < 0.07] in these different tests, except a marginal side x transgene x treatment interaction in stepping test [F_{(1, 44)} = 3.55, P = 0.07, partial η² = 0.07] and a transgene x treatment interaction in LDA [F_{(1, 44)} = 3.68, P = 0.06, partial η² = 0.08], mainly driven by small size effects related to the transgene condition and not to a C21 effect on hM4Di rats. Data are expressed as mean ± SEM. Bonferroni correction post-hoc analysis: ***, P < 0.001.