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. 2020 Jan 14;88(1):77–84. doi: 10.1038/s41390-019-0728-6

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Flow diagram of within-litter randomization to treatment groups for Experiments 1 and 2. Experiment 1: Establish the antenatal methadone-dependent and neonatal acute withdrawal model. Treatment groups: NAL OD: methadone-exposed, opioid-dependent pups, naloxone-precipitated acute withdrawal; SAL OD: methadone-exposed, opioid-dependent pups, no naloxone; and Sham: saline exposed, no opioid dependence, no naloxone. Experiment 2: NAC effects on acute withdrawal behaviors and CNS metabolism. Treatment groups: NAC/NAL OD: methadone-exposed, opioid-dependent pups, NAC, naloxone-precipitated acute withdrawal; SAL/NAL OD: methadone-exposed, opioid-dependent pups, no NAC, naloxone-precipitated acute withdrawal; and Sham: saline exposed, no opioid dependence, no NAC, no naloxone. b Experiment timeline.