Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, 19615-1178, Tehran, Iran.
Brain Res Bull. 2019 Mar;146:237-243. doi: 10.1016/j.brainresbull.2019.01.013. Epub 2019 Jan 17.
Increased vulnerability to drug abuse has been observed after exposure to stress and the prefrontal cortex (PFC) plays a major role in the control of the stress response and reward pathway. The current study was conducted to clarify the effects of acute and chronic restraint stress on PFC neural activity during the reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. Following the establishment of CPP (METH 0.5 mg/kg; s.c. for 3 days) and the extinction phase, male Wistar rats were divided into threshold (0.25 mg/kg; s.c.) and sub-threshold (0.125 mg/kg; s.c.) METH-treated super groups to induce reinstatement. Each super group contained control (non-stressed), acute restraint stress (ARS) and chronic restraint stress (CRS) groups. in vivo single unit recordings were performed on the urethane-anesthetized rats in these groups. After baseline recordings (10-min period) of the neurons in the PFC, their firing activity was recorded for 50 min during the reinstatement phase after injection of METH. The results showed that the threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the non-stressed animals. The sub-threshold dose of METH notably changed this activity in both the ARS and CRS groups. These changes in the excited neurons after the sub-threshold dose in the ARS and CRS groups were significantly higher than those in the non-stressed group. It appears that the PFC is implicated in the associated reward pathway and stress functions. METH affected the firing rate of PFC neurons and stress amplified the effect of METH on changes in the neuronal firing rate in the PFC.
在暴露于应激后，人们观察到对药物滥用的易感性增加，而前额叶皮层（PFC）在控制应激反应和奖励途径中起着重要作用。本研究旨在阐明急性和慢性束缚应激对大鼠中诱导的甲基苯丙胺（METH）条件位置偏爱（CPP）复燃期间 PFC 神经活动的影响。在 CPP 建立（METH 0.5mg/kg；皮下 3 天）和消退阶段之后，雄性 Wistar 大鼠被分为阈剂量（0.25mg/kg；皮下）和亚阈剂量（0.125mg/kg；皮下）METH 处理的超级组以诱导复燃。每个超级组包含对照（未应激）、急性束缚应激（ARS）和慢性束缚应激（CRS）组。在这些组的乌拉坦麻醉大鼠上进行了体内单细胞记录。在 PFC 神经元的基线记录（10 分钟期间）之后，在 METH 注射后的复燃阶段期间记录了 50 分钟的神经元放电活动。结果表明，阈剂量但不是亚阈剂量的 METH 显著增加了非应激动物的 PFC 神经活动。亚阈剂量的 METH 在 ARS 和 CRS 组中显著改变了这种活动。ARS 和 CRS 组中，亚阈剂量后兴奋神经元的这些变化明显高于非应激组。看来，PFC 参与了相关的奖励途径和应激功能。METH 影响了 PFC 神经元的放电率，而应激放大了 METH 对 PFC 神经元放电率变化的影响。
