Timár Julia, Sobor Melinda, Király Kornél P, Gyarmati Susanna, Riba Pál, Al-Khrasani Mahmoud, Fürst Susanna
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Behav Pharmacol. 2010 Feb;21(1):58-68. doi: 10.1097/FBP.0b013e3283359f39.
This study investigated the behavioural consequences of peri, pre and postnatal morphine (MO) exposure in rats. From gestational day 1 dams were treated with either saline or MO subcutaneously once a day (5 mg/kg on the first 2 days, 10 mg/kg subsequently). Spontaneous locomotor activity in a new environment (habituation) and antinociceptive effects of MO were measured separately in male and female pups after weaning and also in late adolescence or adulthood. The rewarding effect of MO was assessed by conditioned place preference in adult animals. Both exposure-induced and sex differences were observed. A significant delay in habituation to a new environment and decreased sensitivity to the antinociceptive effect of MO were found in male offspring of MO-treated dams. In contrast, the place preference induced by MO was enhanced in the MO-exposed adult animals and this effect was more marked in females. Prenatal exposure to MO resulted in more marked changes than the postnatal exposure through maternal milk. The results indicate that a medium MO dose administered once-daily results in long-term consequences in offspring and may make them more vulnerable to MO abuse in adulthood.
本研究调查了围产期、产前和产后吗啡（MO）暴露对大鼠行为的影响。从妊娠第1天起，母鼠每天皮下注射一次生理盐水或MO（前2天为5mg/kg，随后为10mg/kg）。断奶后以及青春期后期或成年期，分别测量了雄性和雌性幼崽在新环境中的自发运动活动（习惯化）以及MO的抗伤害感受作用。通过成年动物的条件性位置偏爱评估了MO的奖赏效应。观察到了暴露诱导的差异和性别差异。在接受MO处理的母鼠的雄性后代中，发现对新环境的习惯化显著延迟，并且对MO的抗伤害感受作用的敏感性降低。相比之下，在暴露于MO的成年动物中，MO诱导的位置偏爱增强，并且这种效应在雌性中更为明显。产前暴露于MO比通过母乳进行的产后暴露导致的变化更为显著。结果表明，每天一次给予中等剂量的MO会对后代产生长期影响，并可能使它们在成年期更容易滥用MO。
