Norioun Hamid, Jamal Moshtaghian Seyed, Alavian Firoozeh, Khombi Shooshtari Maryam, Alipour Golnaz, Ghiasvand Saeedeh
Medical Genetics Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Int J Reprod Biomed. 2024 Sep 12;22(7):579-592. doi: 10.18502/ijrm.v22i7.16971. eCollection 2024 Jul.
Opioid analgesics like morphine and methadone are widely used for managing severe pain; however, concerns over their potential misuse and adverse effects on the brain and reproductive system are significant.
We aimed to investigate their impacts on spermatogenesis and cognitive function in male Norway rats.
In this experimental study, 36 male Norway rats (250-300 gr, 6 months old) were divided into 6 groups: low-dose morphine, high-dose morphine, low-dose methadone, high-dose methadone, positive control (received normal saline at 5 mg/kg), and negative control (received no treatment). Morphine and methadone were administered intraperitoneally over 30 days at doses of 3 mg/kg and 7 mg/kg, respectively. Behavioral assessments evaluated anxiety, stress, and short- and long-term memory. Sperm parameters (viability, motility, morphology), hormonal analysis (testosterone, luteinizing hormone, follicle-stimulating hormone, estradiol), and gene expressions () were assessed.
A significant reduction in rat weight was observed in the high-dose morphine group (p = 0.0045), while testicular weights remained unchanged. Sperm abnormalities were observed with high doses of methadone and morphine. High-dose methadone significantly reduced offspring count (p = 0.0004). Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol varied significantly across treatment groups. Gene expression was altered in response to treatments (p 0.05).
Prolonged exposure to methadone and morphine resulted in memory dysfunction, chronic stress, hormonal disturbances, altered gene expression, and fertility complications. These effects were more pronounced at higher doses, highlighting the importance of careful dosage management in opioid therapy.
吗啡和美沙酮等阿片类镇痛药被广泛用于管理重度疼痛；然而，对其潜在滥用以及对大脑和生殖系统的不良影响的担忧颇为显著。
我们旨在研究它们对雄性挪威大鼠精子发生和认知功能的影响。
在这项实验研究中，36只雄性挪威大鼠（250 - 300克，6个月大）被分为6组：低剂量吗啡组、高剂量吗啡组、低剂量美沙酮组、高剂量美沙酮组、阳性对照组（接受5毫克/千克生理盐水）和阴性对照组（未接受任何治疗）。吗啡和美沙酮分别以3毫克/千克和7毫克/千克的剂量腹腔注射30天。行为评估包括焦虑、应激以及短期和长期记忆。评估了精子参数（活力、运动性、形态）、激素分析（睾酮、黄体生成素、卵泡刺激素、雌二醇）以及基因表达（）。
高剂量吗啡组大鼠体重显著降低（p = 0.0045），而睾丸重量保持不变。高剂量美沙酮和吗啡组观察到精子异常。高剂量美沙酮显著降低了后代数量（p = 0.0004）。各治疗组之间卵泡刺激素、黄体生成素、睾酮和雌二醇水平差异显著。基因表达因治疗而改变（p < 0.05）。
长期接触美沙酮和吗啡会导致记忆功能障碍、慢性应激、激素紊乱、基因表达改变以及生育并发症。这些影响在高剂量时更为明显，凸显了阿片类药物治疗中谨慎剂量管理的重要性。
