Extended abstinence from morphine normalizes sperm small RNA expression and prevents transmission of multigenerational phenotypes

We examined the impact of paternal abstinence following morphine self_administration on the transmission of multigenerational factors from the F0 to the F1 generation. Previously, we found that offspring of non_abstinent, morphine administering male rats showed increased morphine_taking, diminished adolescent social play, and reduced sensitivity to morphine analgesia. Here, we show that these phenotypes are normalized in the offspring of fathers who were 90 days abstinent from morphine at the time of breeding. We further compared the small RNA content of sperm collected from non_abstinent versus 90 days abstinent F0 males to identify candidate molecules correlated with transmission of morphine_induced multigenerational phenotypes. Mature sperm collected from cauda epididymus of male rats from 4 experimental treatment groups: Morphine IVSA, no abstinence; Morphine IVSA + abstinent 90 days; Saline IVSA, no abstinence; Saline IVSA + abstinent 90 days.