BACKGROUND Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin. METHODS Male Sprague-Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague-Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring. RESULTS Heroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2. CONCLUSION Our results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.

中文翻译：

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父本海洛因成瘾对男性后代焦虑和攻击行为的跨代影响。

背景技术海洛因成瘾日益受到关注，影响了许多国家的社会经济发展。关于海洛因成瘾对表型变化的转基因作用知之甚少。这项研究旨在调查由于父亲暴露于海洛因而引起的多达四代成年雄性大鼠的焦虑和攻击水平的变化。方法雄性Sprague-Dawley大鼠在腹腔内（ip）每天两次海洛因暴露，剂量递增（F0-海洛因），持续14天。将雄性Sprague-Dawley大鼠（6周龄）分为：（1）海洛因暴露组（F0-海洛因）和（2）用盐溶液处理的对照组（F0-对照）。剂量方案以每天最低剂量的海洛因3毫克/千克开始，然后以每天1.5毫克/千克的增量递增，直到最终剂量为每天13.5毫克/千克。在出生后的第21天，给后代断奶。在海洛因缺乏2周后，将每代成年的雄性后代与未成年雌性大鼠进行交配。使用开场测试和高架迷宫测试来研究焦虑水平，而常驻入侵者测试用于评估成瘾雄性大鼠及其后代的攻击水平。结果与对照组相比，雄性大鼠海洛因暴露导致产仔数更小。与对照大鼠相比，我们观察到海洛因暴露大鼠（F0）所引起的F1和F2后代的焦虑水平更高。与对照相比，父本海洛因暴露也导致F1的侵略性子代明显更多。在F2中也观察到了相同的模式。