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可能涉及伏隔核 D1 样多巴胺受体在吗啡戒断大鼠子代吗啡诱导的条件性位置偏爱中的作用。

Possible involvement of nucleus accumbens D1-like dopamine receptors in the morphine-induced condition place preference in the offspring of morphine abstinent rats.

机构信息

Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Life Sci. 2019 Sep 15;233:116712. doi: 10.1016/j.lfs.2019.116712. Epub 2019 Aug 1.

Abstract

AIMS

Previous researches demonstrated that genetics and environment are two essential factors to prone individuals to drug abuse. Our previous data showed that dopaminergic system changed in the offspring of morphine-abstinent rats. In the present study, we evaluated whether blocking the D1-like dopamine receptors (DR) in the nucleus accumbens (NAC) affect the rewarding effect of morphine in the offspring of morphine-abstinent rats.

MAIN METHODS

In the study, male and female Wistar rats received morphine orally for 21 days. Ten days after last morphine administration, animals prepared to mate either with a morphine abstinent or a drug-naive rat. Adult male offspring were chosen for further evaluation. SCH23390 (0.01 μg/rat) was administrated intra-NAC during the conditioning phase in the CPP paradigm (morphine 7.5 mg/kg).

KEY FINDINGS

Obtained data showed that morphine administration (7.5 mg/kg) did not induce conditioning in the offspring of the morphine-abstinent parent(s) (p < 0.001) compared with the control group. However, when SCH23390 injected in the NAC during the induction phase, the offspring of morphine-abstinent rats were conditioned with the same dose of morphine.

SIGNIFICANCE

Previous studies showed that the offspring of morphine-abstinent rats are more prone to opioid consumption, and also developed tolerance to the rewarding effect of morphine. Current data indicated that blockade of D1-like DR in the NAC could prevent morphine-induced tolerance in these offspring. Therefore, inhibition of D1-like DR in the NAC might be a new candidate against morphine-reinforcing effect in the offspring of morphine-abstinent parent(s).

摘要

目的

先前的研究表明,遗传和环境是导致个体易滥用药物的两个重要因素。我们之前的数据显示,吗啡戒断大鼠的后代多巴胺能系统发生了变化。在本研究中,我们评估了阻断伏隔核(NAC)中的 D1 样多巴胺受体(DR)是否会影响吗啡戒断大鼠后代对吗啡的奖赏效应。

主要方法

在这项研究中,雄性和雌性 Wistar 大鼠口服给予吗啡 21 天。末次吗啡给药 10 天后,动物准备与吗啡戒断或药物未处理的大鼠交配。选择成年雄性后代进行进一步评估。SCH23390(0.01μg/大鼠)在 CPP 范式(吗啡 7.5mg/kg)的条件期内经 NAC 内给药。

主要发现

获得的数据表明,与对照组相比,吗啡(7.5mg/kg)给药不会诱导吗啡戒断父母的后代产生条件反射(p<0.001)。然而,当 SCH23390 在诱导期内注射到 NAC 中时,吗啡戒断大鼠的后代用相同剂量的吗啡产生了条件反射。

意义

先前的研究表明,吗啡戒断大鼠的后代更容易吸食阿片类药物,并且对吗啡的奖赏效应产生了耐受性。目前的数据表明,阻断 NAC 中的 D1 样 DR 可以防止这些后代对吗啡诱导的耐受。因此,抑制 NAC 中的 D1 样 DR 可能是对抗吗啡戒断父母后代中吗啡强化作用的新候选药物。

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