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Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring

机译：父本海洛因成瘾对男性后代焦虑和攻击行为的跨代影响

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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-na?ve 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.
机译：背景海洛因成瘾日益引起人们的关注，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了解甚少。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程度的变化。方法雄性Sprague-Dawley大鼠每天两次腹膜内（i.p.）暴露于海洛因，持续14天，并增加剂量（F0-海洛因）。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）盐溶液治疗的对照组（F0-对照组）。剂量方案开始于海洛因的最低剂量为每天3？mg / kg，随后以每天1.5？mg / kg的增量递增，最终剂量为每天13.5？mg / kg。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幼稚的大鼠进行交配。使用开场试验和高架迷宫试验研究焦虑水平，而使用常驻入侵者试验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减少。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的侵略性子代显着增加。在F2中也观察到了相同的模式。结论我们的结果表明F1和F2的后代持续较高水平的焦虑和攻击性，这是由于父亲海洛因暴露引起的。

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