The ongoing opioid addiction crisis necessitates the identification of novel risk factors to improve prevention and treatment of opioid use disorder. Parental opioid exposure has recently emerged as a potential regulator of offspring vulnerability to opioid misuse, in addition to heritable genetic liability. An understudied aspect of this “missing heritability” is the developmental presentation of these cross-generational phenotypes. This is an especially relevant question in the context of inherited addiction-related phenotypes, given the prominent role of developmental processes in the etiology of psychiatric disorders. Paternal morphine self-administration was previously shown to alter the sensitivity to the reinforcing and antinociceptive properties of opioids in the next generation. Here, phenotyping was expanded to include the adolescent period, with a focus on endophenotypes related to opioid use disorders and pain. Paternal morphine exposure did not alter heroin or cocaine self-administration in male and female juvenile progeny. Further, baseline sensory reflexes related to pain were unaltered in morphine-sired adolescent rats of either sex. However, morphine-sired adolescent males exhibited a reduction in social play behavior. Our findings suggest that, in morphine-sired male offspring, paternal opioid exposure does not affect opioid intake during adolescence, suggesting that this phenotype does not emerge until later in life. Altered social behaviors in male morphine-sired adolescents indicate that the changes in drug-taking behavior in adults sired by morphine-exposed sires may be due to more complex factors not yet fully assessed.

持续存在的阿片类药物成瘾危机需要识别新的危险因素，以改善阿片类药物使用障碍的预防和治疗。除了遗传倾向之外，父母接触阿片类药物最近已成为后代容易滥用阿片类药物的潜在调节因素。这种“遗传性缺失”的一个未被充分研究的方面是这些跨代表型的发育表现。鉴于发育过程在精神疾病病因学中的突出作用，在遗传成瘾相关表型的背景下，这是一个特别相关的问题。此前研究表明，父亲自我给药吗啡会改变下一代对阿片类药物的增强和镇痛特性的敏感性。在这里，表型分析扩展到包括青少年时期，重点关注与阿片类药物使用障碍和疼痛相关的内表型。父亲的吗啡暴露不会改变雄性和雌性青少年后代的海洛因或可卡因自我给药情况。此外，在使用吗啡的雄性青春期大鼠中，与疼痛相关的基线感觉反射没有改变。然而，服用吗啡的青少年男性表现出社交游戏行为的减少。我们的研究结果表明，在吗啡生育的男性后代中，父亲的阿片类药物暴露不会影响青春期阿片类药物的摄入，这表明这种表型直到晚年才会出现。服用吗啡的雄性青少年的社会行为改变表明，暴露于吗啡的雄性后代的成年吸毒行为的变化可能是由于尚未完全评估的更复杂的因素造成的。