Fig. 4. VGLUT3T8I/T8I mice exhibit normal locomotor activity and anxiety phenotype but show increased vulnerability to cue-induced reinstatement of cocaine seeking compared to controls.
a, Horizontal locomotor activity of WT mice (black) or VGLUT3T8I/T8I mice (purple) measured during a complete day-night cycle (p = 0.776, two-way RM ANOVA). b-d, Elevated plus maze (n = 12 WT mice and n = 12 VGLUT3T8I/T8I mice). b, Number of entries in closed or open arms c, Time spent in open arms versus closed arms (%). d, Number of transitions from closed (c) to open (o) arms. e, Marble-burying test. Statistical analyses were performed with two-way RM ANOVA and post hoc comparison with Bonferroni’s test (a,e) and two-sided unpaired t-test (b-d). f-j, Cocaine (0.5 mg.kg−1 per infusion, iv) self-administration in WT mice (black, n = 14 mice) or VGLUT3T8I/T8I mice (purple, n = 11 mice). f, Number of active nosepokes during the acquisition (fixed ratio 1 (FR1) and 3 (FR3)) of self-administration. genotype x time F9,207 = 0.972, p = 0.464, two-way RM ANOVA. g, Percentage of mice reaching the criteria for operant conditioning learning. * p = 0.010 (two-sided chi-squared test). h, Motivation for cocaine measured by the breaking point achieved in the progressive ratio schedule of reinforcement (two-sided unpaired t-test, p = 0.60). i, Number of active nosepokes during extinction procedure (genotype x time, F21,483 = 0.7128, p = 0.8215, two-way RM ANOVA). j, Cue-induced reinstatement with the mean number of active nosepokes during the different experimental phases: acquisition of cocaine self-administration behavior (mean of 3 days acquisition criteria), extinction (mean of 3 days extinction criterion) and reinstatement induced by cues. Number of active nosepokes during cue-induced reinstatement test (two-sided unpaired t-test, * p = 0.041). Data are presented as mean values ± SEM in a-j. Source data are provided as a Source Data file.