Figure 1.

Experimental timeline. Perinatal morphine treatment to mouse dams (MO, 10 mg/kg, s.c.) versus SAL began 7 d before breeding [gestational day 7 (GD-7), start of the study], continued through birth and lactation until offspring were weaned on P21. Maternal plasma was collected on P22 for LC-MS/MS, 20 h after the final MO injection. One cohort of mouse offspring was used for P21 gene expression. A second behaviorally naive cohort was used for immunohistochemistry at 23 weeks (w) of age. The third cohort underwent testing for three-chambered social interaction, sucrose/high-fat diet preference, and operant testing (FR1; PR, progressive ratio), and brains were used for gene expression at 22 weeks. Finally, a smaller separate cohort of dams were injected at GD14–GD18, and maternal plasma, placentas, and fetal brains were collected at 1 and 4 h after MO injection for LC-MS/MS. Refer to Extended Data Figure 1-1 for sample sizes, and Extended Data Figures 1-2, 1-3, 1-4 for gene expression targets. Refer to Extended Data Figures 1-5, 1-6, 1-7 for additional birthing and offspring outcomes.