Opioid addiction causes some molecular alterations in the brain reward pathway, such as changes in gene expression that may be transferred to the next generation via epigenetic mechanisms such as histone acetylation. This study aimed to evaluate the effect of theophylline as an HDAC (Histone deacetylases) activator on D1 and D2 dopamine receptor expression in the nucleus accumbens (NAc) and anxiety behavior in the offspring of morphine-dependent female rats. Female rats were exposed to escalating doses of morphine for six days and were then treated with theophylline (20 mg/kg) or saline for 10 days before mating with normal male rats. Male and female offspring were tested for anxiety behavior using an elevated plus maze apparatus. Besides, the expression of D1 and D2 dopamine receptors in the NAc was evaluated by real-time PCR (polymerase chain reaction). Results showed that offspring of morphine-dependent female rats had increased expression of both D1 and D2 receptors in the NAc, as well as increased anxiety behavior, compared to control offspring. However, the mentioned effects were returned to normal levels in the offspring whose morphine-dependent mothers had received theophylline for 10 days before mating. It is concluded that theophylline may be therapeutically effective in minimizing the adverse consequences of maternal morphine dependence on offspring behavior by restoring normal dopamine receptor expression levels and lowering anxiety. To completely comprehend the underlying mechanisms of this phenomenon, more research is required.

阿片类药物成瘾会导致大脑奖赏通路发生一些分子改变，例如基因表达的变化，这些变化可能通过组蛋白乙酰化等表观遗传机制转移到下一代。本研究旨在评估茶碱作为 HDAC（组蛋白脱乙酰酶）激活剂对伏核 (NAc) 中 D1 和 D2 多巴胺受体表达以及吗啡依赖性雌性大鼠后代焦虑行为的影响。雌性大鼠暴露于逐渐增加剂量的吗啡六天，然后用茶碱 (20 mg/kg) 或生理盐水治疗 10 天，然后与正常雄性大鼠交配。使用高架十字迷宫装置测试雄性和雌性后代的焦虑行为。此外，通过实时PCR（聚合酶链式反应）评估NAc中D1和D2多巴胺受体的表达。结果显示，与对照后代相比，吗啡依赖雌性大鼠的后代 NAc 中 D1 和 D2 受体的表达增加，焦虑行为也增加。然而，吗啡依赖性母亲在交配前服用茶碱 10 天后，其后代的上述影响恢复到正常水平。结论是，茶碱可能通过恢复正常的多巴胺受体表达水平和降低焦虑，在治疗上有效地减少母体吗啡依赖对后代行为的不利影响。要完全理解这种现象的根本机制，需要更多的研究。