Maternal toxicant exposure during gestation can have deleterious effects on neurobehavioral development of the offspring. The potential risks engendered by paternal toxicant exposure prior to conception have been largely understudied. Recently, we found that chronic THC exposure prior to conception in male rats causes long-lasting behavioral impairment in their offspring. The current study examined the effects of chronic preconception exposure to cannabis smoke extract in Sprague-Dawley rats at two different phases in sperm development. One group received daily subcutaneous (sc) injections of THC in cannabis extract at 4 mg/kg/day for 28 days until three days prior to mating with untreated females (late exposure group). Another group received the same regimen except they underwent 56 days of drug abstinence prior to mating (early exposure group). These were compared with a control group treated with vehicle. The offspring underwent a battery of tests for behavioral function to assess motor, emotional and cognitive function. On the elevated plus maze test, the offspring of both paternal cannabis smoke extract (CSE) exposure groups had significantly more time on the open arms than control offspring, indicative of greater risk-taking behavior. No significant main effects of CSE exposure were seen on adolescent or adult locomotor activity in the figure-8 apparatus. In the novel object recognition test, there was a significantly greater drop-off in novel object preference across the session in the male, but not female offspring of the late exposure group. There was also a sex-selective effect of paternal CSE treatment in the 16-arm radial maze test of memory function. Female offspring of the late exposure group had significantly more working memory errors than control females in the first half of the 12-session training sequence. No significant effects were seen in the operant visual signal sustained detection test of attention. This study shows that there are long-lasting behavioral consequences of preconception CSE exposure through the paternal lineage in rats.

妊娠期间母体毒物暴露会对后代的神经行为发育产生有害影响。受孕前父亲暴露于有毒物质所产生的潜在风险在很大程度上尚未得到充分研究。最近，我们发现雄性大鼠在受孕前长期暴露于 THC 会导致其后代的长期行为障碍。目前的研究检查了 Sprague-Dawley 大鼠在精子发育的两个不同阶段长期接触大麻烟雾提取物的影响。一组每天皮下 (sc) 注射大麻提取物中的四氢大麻酚，剂量为 4 毫克/公斤/天，持续 28 天，直到与未治疗的雌性交配前三天（晚期暴露组）。另一组接受相同的方案，只是他们在交配前接受了 56 天的禁药（早期暴露组）。将这些与用载体处理的对照组进行比较。后代接受了一系列行为功能测试，以评估运动、情绪和认知功能。在高架十字迷宫测试中，两个父系大麻烟提取物 (CSE) 暴露组的后代比对照组的后代在张开臂上的时间明显多于对照组，这表明他们有更大的冒险行为。在图 8 装置中未观察到 CSE 暴露对青少年或成人运动活动的显着主要影响。在新物体识别测试中，男性后代的新物体偏好在整个会话中显着下降，但晚期暴露组的女性后代没有。在记忆功能的 16 臂径向迷宫测试中，父亲 CSE 治疗也存在性别选择性效应。在 12 次训练序列的前半部分，晚期暴露组的雌性后代的工作记忆错误明显多于对照组雌性。在操作性视觉信号持续检测注意力测试中没有发现显着影响。这项研究表明，通过大鼠的父系血统，孕前 CSE 暴露会产生长期的行为后果。