Fig. 3: Pharmaco-fUSI reveals a sex-dependence of opioid-mediated effects of ketamine administration.

a Rats received an s.c. injection of either vehicle (VEH; saline) or naltrexone (NTX; 10 mg/kg) followed by ketamine (KET; 10 mg/kg, i.v.) or vehicle after 10 min. Each animal was imaged three times under the treatment conditions of VEH + KET, NTX + KET, and NTX + VEH. b, c Functional maps in male (b) and female (c) rats. The t scores were calculated by contrasting the pixel-wise peak cerebral blood volume (CBV) in the NTX + KET versus VEH + KET groups. Statistically significant clusters are displayed overlaid on a power Doppler template (one cohort of n = 9 females and n = 9 males imaged at bregma +2.5 mm; one cohort of n = 9 females and n = 9 males imaged at bregma −3.5 mm; two-tailed paired t-test, corrected P < 0.05). In male rats, functional maps show that naltrexone reduced peak activity in M1/2, Cg1, NAc, and CPu, and increased activity in RSG, LHb, and LPRL. There were only minor clusters in female rats. d, e CBV time series in Cg1, Cpu, NAcC, RSG, and LHb in male (d) and female (e) rats. Solid lines represent the mean values and shaded areas are SEM. f A different cohort of male rats received an i.v. dose of 0.1 mg/kg MK-801 with naltrexone or vehicle pretreatment. The bar plots display the peak CBV in the Cg1 and NAcC regions. Two-tailed paired t-tests (NTX + KET vs VEH + KET and NTX + MK-801 vs VEH + MK-801), corrected P: Cg1 = 0.016 (KET), 0.572 (MK-801); NAcC = 0.024 (KET), 0.922 (MK-801). Hedge’s g effect sizes: Cg1 = −1.2 (KET), −0.3 (MK-801); NAcC = −0.97 (KET), 0.04 (MK-801). n = 9 male rats (KET groups); n = 6 male rats (MK-801 groups). Data are presented as mean +/− SEM. g CBV time series in Cg1 and NAcC in male rats receiving MK-801. n = 6 male rats. Solid lines represent the mean values and shaded areas are SEM. Source data are provided as a Source Data file. Details on the statistical analyses are provided in Supplementary Table 1.