Molecular Medicine Research Centre, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Neuroscience Research Center, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran.
Behav Brain Res. 2014 May 1;264:43-50. doi: 10.1016/j.bbr.2014.01.045. Epub 2014 Feb 5.
Addiction is a common psychiatric disease and stress has an important role in the drug seeking and relapse behaviors. The involvement of basolateral amygdala (BLA) in the effects of stress on reward pathway is discussed in several studies. In this study, we tried to find out the involvement of glucocorticoid receptors (GRs) in the BLA in stress-induced reinstatement of extinguished morphine-induced conditioned place preference (CPP) in rats. The CPP paradigm was done in adult male Wistar rats weighing 220-320 g, and conditioning score and locomotor activity were recorded by Ethovision software. Animals received effective dose of morphine (5mg/kg) daily, during the 3-day conditioning phase. In extinction phase, rats were put in the CPP box for 30 min a day for 8 days. After extinction, animals were injected by corticosterone (10 m/kg) or exposed to forced swim stress (FSS) 10 min before subcutaneous administration of ineffective dose of morphine (0.5mg/kg) in order to reinstate the extinguished morphine-CPP. To block the glucocorticoid receptors in the BLA, after stereotaxic surgery and placing two cannulae in this area bilaterally, animals received GR antagonist mifepristone (RU38486; 0.3, 3 and 30 ng/0.3 μl DMSO per side) prior to exposure to FSS then each animal received ineffective dose of morphine (0.5mg/kg) as drug-induced reinstatement. The results revealed that physical stress (FSS) but not exogenous corticosterone can significantly induce reinstatement of extinguished morphine-CPP, and intra-BLA mifepristone prevents the stress-induced reinstatement. It can be proposed that stress partially exerts its effect on the reward pathway via glucocorticoid receptors in the BLA.
成瘾是一种常见的精神疾病，压力在觅药和复吸行为中起着重要作用。几项研究探讨了外侧杏仁核（BLA）在压力对奖励通路的影响中的作用。在这项研究中，我们试图找出 BLA 中的糖皮质激素受体（GRs）在压力诱导的已消退的吗啡诱导的条件性位置偏好（CPP）在大鼠中的重新出现中的作用。CPP 范式在成年雄性 Wistar 大鼠中进行，体重为 220-320g，通过 Ethovision 软件记录条件评分和运动活动。动物接受有效剂量的吗啡（5mg/kg），在 3 天的条件期内。在消退期，大鼠每天在 CPP 箱中放置 30 分钟，共 8 天。消退后，动物在皮下给予无效剂量的吗啡（0.5mg/kg）前 10 分钟给予皮质酮（10m/kg）或强迫游泳应激（FSS），以重新出现已消退的吗啡-CPP。为了阻断 BLA 中的糖皮质激素受体，在立体定向手术后，在双侧放置两个套管，动物在暴露于 FSS 之前接受 GR 拮抗剂米非司酮（RU38486；0.3、3 和 30ng/0.3μl DMSO 每侧），然后每只动物接受无效剂量的吗啡（0.5mg/kg）作为药物诱导的重新出现。结果表明，躯体应激（FSS）而不是外源性皮质酮可以显著诱导已消退的吗啡-CPP 的重新出现，而 BLA 内的米非司酮可预防应激诱导的重新出现。可以提出，压力通过 BLA 中的糖皮质激素受体部分对奖励通路产生影响。
