Fig.5: Effects of PGE2 receptor stimulation on DS neurons activity and mouse behavior.

a-c. Misoprostol pretreatment does not alter D1 neurons Ca²⁺ activity during exploration of a novel environment (new cage). The activity was evaluated by fiber photometry in the DS of Drd1-Cre mice stereotactically injected with an AAV GCaMP6f (Supplementary Fig.10a–c). Each mouse was recorded twice with an interval ≥ 1 day, 30 min after receiving either vehicle (Veh) or misoprostol (Miso, 0.1 mg.kg⁻¹, i.p.). a. Average traces of mice injected with vehicle and placed for 1 min in a novel environment. b. Same as in a for mice injected with misoprostol. c. Plot of the area under the curve (AUC) in a and b during the novel environment exploration (60 s) minus the AUC during baseline (50 s), 10 mice per group. Mann-Whitney test, p = 0.39. d-f. Misoprostol decreases Ca²⁺ responses to change in environment in D2 neurons. Same experiment as in a-c but in Drd2-Cre mice injected with vehicle (d, n = 10) or misoprostol (e, n = 9). Mann-Whitney test, p = 0.043. g. The effects of PGE2 receptors stimulation on DRD2 function were investigated by evaluating the immobility 45-180 min after haloperidol injection (0.1 mg.kg⁻¹, i.p.), in mice pretreated 15 min before haloperidol with misoprostol (0.1 mg.kg⁻¹, i.p.) or vehicle (9 mice per group). The same experiment was run twice on different groups of mice with results similar to the one shown here. 2-way repeated measures-ANOVA (RM-ANOVA), misoprostol and time effects, both p<10⁻⁴. h, i. Effects of chronic misoprostol on procedural learning and reversal. (h) Wild-type male mice were implanted with an i.p. osmopump delivering vehicle (20 mice) or misoprostol (24 mice). Acquisition and reversal of the food-rewarded arm choice in a Y maze was tested 20-25 days later. RM-ANOVA, misoprostol effect, learning phase, not significant, reversal, p=2.10⁻⁴. (i) Same as h except that osmopump infusion bilaterally delivered into the DS vehicle (10 mice) or misoprostol (9 mice). 2-way RM-ANOVA, misoprostol effect, learning phase, p=0.003, reversal, p=0.002. g-i, multiple comparison Holmes-Sidak’s tests, *p < 0.05, **p < 0.01, ***p<0.001, **** p<10⁻⁴. See Supplementary Table 19 for detailed statistical results.