Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism
Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism
复制标题
DOI：
10.1016/j.drugalcdep.2018.03.024
复制
发表时间：
2018-06-01
影响因子：
4.2
通讯作者：
Woodlen, Kristin
中科院分区：
文献类型：
--
作者：
Ball, Kevin T.;Stone, Eric;Woodlen, Kristin
背景：治疗可卡因成瘾患者的一个主要障碍是他们有很高的复发倾向。虽然急性应激诱发复发的临床情景在动物模型中已经得到了很好的研究，但很少有临床前研究探讨慢性应激在复发中的作用，或者慢性应激与其他复发诱因之间的相互作用。方法：我们使用基于灭绝和戒断的动物复发模型来测试慢性束缚应激对大鼠寻找可卡因的影响。训练大鼠按下杠杆，静脉注射可卡因(0.50 mg/kg/次)，并在每天3小时的会议中配合离散的音调+光线提示。在自我给药后，在13天消退期的前7天，大鼠暴露于慢性束缚应激程序(3小时/天)或控制程序(非应激)中，在此期间，杠杆按压没有程序性后果。紧随其后的是线索和可卡因引发的药物寻找测试。结果：慢性束缚应激史与可卡因刺激诱导的寻求增加有关，这种作用可被多巴胺D-1受体拮抗剂SCH-23390(10.0mg/kg)与每日束缚联合使用而减弱。结论：戒断早期暴露于慢性应激可能使某些类型的复吸行为持续易感，多巴胺D-1样受体似乎在慢性应激对寻求可卡因的影响和戒断过程中起中介作用。
Background: A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers.Methods: We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/ kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure.Results: A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 mu g/kg; i.p.), a dopamine D-1-like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement.Conclusions: Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D-1-like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking.