Sadat-Shirazi Mitra-Sadat, Karimi Forough, Kaka Gholamreza, Ashabi Ghorbangol, Ahmadi Iraj, Akbarabadi Ardeshir, Toolee Heidar, Vousooghi Nasim, Zarrindast Mohammad-Reza
Iranian National Center for Addiction Studies.
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine.
Behav Pharmacol. 2019 Aug;30(5):435-445. doi: 10.1097/FBP.0000000000000465.
Opioid addiction is one of the most crucial issues in the world. Opioid abuse by parents makes children more prone to many psychological disorders such as drug addiction. Therefore, this study was carried out to examine the effect of morphine exposure 10 days before gestation on morphine and methamphetamine preference in male offspring. Adult Wistar rats (male and female) received morphine orally for 21 days and were drug free for 10 days. Thereafter, they were allowed to mate with either a morphine-abstinent or drug-naive rat. The male offspring were tested for morphine and methamphetamine preference with a three-bottle choice test. Moreover, the rewarding effects of morphine and methamphetamine were evaluated using a conditioned place preference test. To determine the mechanisms underlying these changes, monoamine oxidase-B (MAO-B) level was measured in the nucleus accumbens (NAC). Offspring of morphine-abstinent mothers and offspring of both-abstinent parents were found to consume morphine more than those of other groups, but in the case of methamphetamine, there were no differences. In addition, the offspring of morphine-abstinent parent(s) did not condition with a high dose of morphine in the conditioned place preference test. Administration of methamphetamine induced conditioning at different doses in controls and offspring of one or two morphine-abstinent parent(s), and there were no effects of parental morphine exposure on the dose of methamphetamine that was required for conditioning. Moreover, the level of MAO-B was increased in the NAC of offspring of morphine-abstinent parents as compared with the control group. These results demonstrate that offspring of a morphine-abstinent mother and a drug-naive father and offspring of two morphine-abstinent parents were more susceptible to opioid but not methamphetamine addiction. Moreover, parental morphine consumption did not have any effect on the reinforcing effect of methamphetamine in their offspring but induced morphine tolerance in the offspring. Although the level of MAO-B was elevated in the NAC, this did not correlate with the methamphetamine preference in offspring.
阿片类药物成瘾是全球最关键的问题之一。父母滥用阿片类药物会使孩子更容易患上许多心理障碍，如药物成瘾。因此，本研究旨在探讨妊娠前10天接触吗啡对雄性后代对吗啡和甲基苯丙胺偏好的影响。成年Wistar大鼠（雄性和雌性）口服吗啡21天，停药10天。此后，让它们与吗啡戒断或未接触过药物的大鼠交配。对雄性后代进行三瓶选择试验以测试其对吗啡和甲基苯丙胺的偏好。此外，使用条件性位置偏爱试验评估吗啡和甲基苯丙胺的奖赏效应。为了确定这些变化背后的机制，测量了伏隔核（NAC）中的单胺氧化酶-B（MAO-B）水平。发现吗啡戒断母亲的后代和父母双方均戒断的后代比其他组消耗更多的吗啡，但在甲基苯丙胺方面，没有差异。此外，在条件性位置偏爱试验中，吗啡戒断父母的后代对高剂量吗啡没有形成条件反射。给予甲基苯丙胺在对照组以及一方或双方吗啡戒断父母的后代中诱导出不同剂量的条件反射，并且父母接触吗啡对形成条件反射所需的甲基苯丙胺剂量没有影响。此外，与对照组相比，吗啡戒断父母的后代伏隔核中MAO-B水平升高。这些结果表明，吗啡戒断母亲和未接触过药物的父亲的后代以及父母双方均吗啡戒断的后代更容易对阿片类药物成瘾，但对甲基苯丙胺成瘾不敏感。此外，父母使用吗啡对其后代甲基苯丙胺的强化作用没有任何影响，但会导致后代对吗啡产生耐受性。虽然伏隔核中MAO-B水平升高，但这与后代对甲基苯丙胺的偏好无关。
