Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Neurotoxicology. 2020 May;78:57-63. doi: 10.1016/j.neuro.2020.01.009. Epub 2020 Feb 8.
The potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation. In an initial study we also showed that a 12-day paternal THC exposure prior to conception alters locomotor activity and impairs cognitive function of their offspring. This study investigated the cross-generational effects of chronic paternal THC exposure in rats (0, 2, or 4 mg/kg/day SC for 28 days) prior to mating with drug naïve females. The offspring of THC-exposed male rats had significant alterations in locomotor activity and cognitive function. Specifically, during adolescence there was significant locomotor hyperactivity in the offspring of males exposed to 2 mg/kg/day of THC. During the novel object recognition task, the controls maintained their relative preference for the novel object across the duration of the ten-min session while the rats whose fathers received THC (2 mg/kg/day) showed a significantly greater drop-off in interest in the novel object during the second half of the session. Learning in the radial-arm maze was significantly delayed in the offspring of males exposed to 4 mg/kg/day of THC. This study shows that premating chronic paternal THC exposure at multiple dose regimens can cause long-lasting detrimental behavioral effects in their offspring, including abnormal locomotor activity and impaired cognitive function. Future studies should investigate the underlying mechanisms driving these aberrant developmental outcomes and seek to identify possible treatments of alleviation in the presence of paternal THC exposure.
大麻的潜在健康风险越来越受到关注，包括对生殖和发育的影响。大量研究调查了母体在妊娠期接触 THC 以及其对后代发育的影响所带来的风险，但关于父体在受孕前接触 THC 的影响的研究甚少。我们之前发现，雄性大鼠接触 THC 会导致精子甲基化发生变化。在一项初步研究中，我们还发现，雄性大鼠在受孕前接受 12 天的 THC 暴露会改变其后代的运动活动和认知功能。本研究调查了慢性父体 THC 暴露（0、2 或 4mg/kg/天 SC，持续 28 天）对大鼠交配前与药物-naive 雌性大鼠的跨代影响。暴露于 THC 的雄性大鼠的后代在运动活动和认知功能方面发生了显著变化。具体来说，在青春期，暴露于 2mg/kg/天 THC 的雄性大鼠的后代表现出明显的运动过度活跃。在新物体识别任务中，对照组在 10 分钟的实验过程中保持对新物体的相对偏好，而其父亲接受了 THC（2mg/kg/天）的大鼠则在实验的后半段对新物体的兴趣明显下降。在接受 4mg/kg/天 THC 的雄性大鼠的后代中，在放射臂迷宫中的学习明显延迟。这项研究表明，在多个剂量方案下，父体在受孕前长期接触 THC 会导致其后代出现持久的有害行为影响，包括运动活动异常和认知功能受损。未来的研究应调查导致这些异常发育结果的潜在机制，并寻求在存在父体 THC 暴露的情况下识别可能的缓解治疗方法。
