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.

中文翻译：

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神经发育毒理学中的父系因素：雄性大鼠THC暴露会对其后代产生长期的神经行为影响。

大麻的潜在健康风险日益受到关注，包括对生殖和发育的影响。广泛的研究已经调查了孕妇在妊娠期间接触四氢大麻酚的风险及其对后代发育的影响，但是关于受孕前父亲四氢大麻酚暴露影响的研究很少。先前我们已经发现，大鼠的父亲THC暴露会导致精子甲基化的改变。在最初的研究中，我们还表明，受孕前12天的父亲THC暴露会改变运动能力并损害其后代的认知功能。这项研究调查了与纯稚雌性交配之前大鼠慢性父本THC暴露（0、2或4 mg / kg /天SC，共28天）的跨代影响。暴露于THC的雄性大鼠的后代在运动能力和认知功能方面有显着改变。具体而言，在青春期期间，暴露于2 mg / kg /天的THC的雄性后代中有明显的运动过度活跃。在识别新物体的过程中，对照组在整个十分钟的训练过程中保持了对新物体的相对偏爱，而父亲接受THC（2 mg / kg /天）的大鼠表现出明显更大的兴趣下降。在课程的下半部分中，该对象处于新颖状态。暴露于4 mg / kg /天THC的雄性后代中，significantly臂迷宫的学习明显延迟。这项研究表明，在多剂量方案下提前长期暴露于父亲的THC会对其后代产生长期的有害行为影响，包括运动活动异常和认知功能受损。未来的研究应调查驱动这些异常发育结果的潜在机制，并寻求确定在父亲THC暴露存在的情况下缓解疾病的可能方法。