Fig. 5: Quantitative analyses in the dorsal striatum, whole striatum and frontal cortex.

A Number of differentially expressed genes (DEG) identified in studies that investigated the striatum (see Fig. S1 for separate analyses of studies that used acute or chronic opioid administration). B Number of DEG in studies of the frontal cortex. C Number of genes identified as differentially expressed (DE) across different studies. D Across the 5 brain regions considered during quantitative analysis, we assessed the impact of the following 7 factors on consistency among studies, using pairwise Jaccard indexes: species, brain structure, treatment chronicity (acute/chronic), opioid drug (morphine/heroin), strain (C57BL6J/others), time of analysis following last exposure (5 lists of DEG from tissue collected 1 h after opioid exposure, 5 after 2 h, 10 after 4 h, 4 after 8 h, 1 after 14 h, and 3 after 24 h) and article. For each factor (e.g., species), pair-wise JI were classified in 2 categories describing whether they belonged to the same sub-group (e.g., 2 studies conducted in humans; “intra”), or not (e.g., 1 study in humans compared to another in rats; “inter”), within that factor. For the drug factor, studies in human were not considered as they cannot be assigned to specific opioids; a single study investigated fentanyl, and was excluded [33]. For the strain factor, among the 14 mouse studies available, JI significantly increased among the 12 that used C57BL6J mice, while a similar analysis was not possible for 129P3/J, DBA/2J, SWR/J or Kunming strains, as only 1 list of DEG was available for each. One study reporting on the combined analysis of C57BL6J and DBA2J mice was excluded [53]. No similar analysis was possible in rats, as all available studies used Sprague-Dawley (except one that did not state the strain used [67]). The number of JI values considered in each comparison are indicated at the bottom of each bar.