Fig. 1: Drd1-cre^120Mxu mice show blunted fentanyl seeking relative to wildtype mice.

A Experimental timeline for self-administration. Following recovery from jugular vein catheter surgery, mice underwent 5 days of fentanyl self-administration training (3 h sessions) under fixed ratio 1 (FR1), followed by 5 days under FR2. Half of the mice underwent a non-reinforced seeking test 24 h after the last self-administration session and the other half underwent seeking 14 d later. B Number of fentanyl infusions (1.5 µg/kg) earned during self-administration training in Drd1-cre^120Mxu (magenta) and wildtype (black) mice during training (wildtype n = 38♀, 48♂; Drd1-cre^120Mxu n = 27♀, 26♂). C Number of active and inactive responses during fentanyl self-administration training. D Discrimination index (active minus inactive responses) during fentanyl self-administration training. E Number of active and inactive responses during a 1h non-reinforced seeking test in wildtype and Drd1-cre^120Mxu mice (**, p = 0.026. Sidak’s post-hoc after 2-way ANOVA. Triangles denote datapoints from males and circles from females). F Number of active and inactive responses during a seeking test in separate mice after 14 days abstinence (*, p = 0.03, Sidak’s post-hoc after 2-way ANOVA). G Experimental timeline for conditioned place preference. Mice freely explored the apparatus for 20 min during the pre-test day. For the following three days, mice received saline (10 mL/kg ip) in one compartment, followed 4 h later by fentanyl (0.2 mg/kg ip) in the other. On the fifth day, mice freely explored the apparatus. H Preference for the fentanyl-paired compartment expressed as time spent in fentanyl-paired chamber during the post-test minus time spent during pre-test (*, p = 0.03, unpaired t-test. Wildtype n = 33♀, 30♂; Drd1- cre^120Mxu n = 33♀, 32♂). I Total number of movement counts during conditioning sessions (*, p = 0.0047, Sidak’s post-hoc after 2-way ANOVA). Data are presented as mean ± SEM with individual mice overlaid.