Kupferschmidt David A, Brown Zenya J, Erb Suzanne
Psychology, University of Toronto Scarborough.
J Vis Exp. 2011 Jan 6(47):2265. doi: 10.3791/2265.
The most insidious aspect of drug addiction is the high propensity for relapse. Animal models of relapse, known as reinstatement procedures, have been used extensively to study the neurobiology and phenomenology of relapse to drug use. Although procedural variations have emerged over the past several decades, the most conventional reinstatement procedures are based on the drug self-administration (SA) model. In this model, an animal is trained to perform an operant response to obtain drug. Subsequently, the behavior is extinguished by withholding response-contingent reinforcement. Reinstatement of drug seeking is then triggered by a discrete event, such as an injection of the training drug, re-exposure to drug-associated cues, or exposure to a stressor. Reinstatement procedures were originally developed to study the ability of acute non-contingent exposure to the training drug to reinstate drug seeking in rats and monkeys. Reinstatement procedures have since been modified to study the role of environmental stimuli, including drug-associated cues and exposure to various forms of stress, in relapse to drug seeking. Over the past 15 years, a major focus of the reinstatement literature has been on the role of stress in drug relapse. One of the most commonly used forms of stress for studying this relationship is acute exposures to mild, intermittent, electric footshocks. The ability of footshock stress to induce reinstatement of drug seeking was originally demonstrated by Shaham and colleagues (1995) in rats with a history of intravenous heroin SA(5). Subsequently, the effect was generalized to rats with histories of intravenous cocaine, methamphetamine, and nicotine SA, as well as oral ethanol SA. Although footshock-induced reinstatement of drug seeking can be achieved reliably and robustly, it is an effect that tends to be sensitive to certain parametrical variables. These include the arrangement of extinction and reinstatement test sessions, the intensity and duration of footshock stress, and the presence of drug-associated cues during extinction and testing for reinstatement. Here we present a protocol for footshock-induced reinstatement of cocaine seeking that we have used with consistent success to study the relationship between stress and cocaine seeking.
药物成瘾最隐匿的方面在于其极高的复发倾向。复发的动物模型，即所谓的复吸程序，已被广泛用于研究药物使用复吸的神经生物学和现象学。尽管在过去几十年中出现了程序上的变化，但最传统的复吸程序是基于药物自我给药（SA）模型。在这个模型中，训练动物做出操作性反应以获取药物。随后，通过停止与反应相关的强化来消除这种行为。然后，由一个离散事件触发对药物寻求行为的恢复，例如注射训练药物、再次暴露于与药物相关的线索或暴露于应激源。复吸程序最初是为了研究急性非条件性接触训练药物恢复大鼠和猴子药物寻求行为的能力而开发的。此后，复吸程序已被修改，以研究环境刺激，包括与药物相关的线索和暴露于各种形式的应激，在药物寻求复吸中的作用。在过去15年中，复吸文献的一个主要焦点是应激在药物复发中的作用。研究这种关系最常用的应激形式之一是急性暴露于轻度、间歇性电足击。足击应激诱导药物寻求行为恢复的能力最初由沙哈姆及其同事（1995年）在有静脉注射海洛因SA史的大鼠中得到证实（5）。随后，该效应推广到有静脉注射可卡因、甲基苯丙胺和尼古丁SA史的大鼠，以及口服乙醇SA的大鼠。尽管足击诱导的药物寻求行为恢复能够可靠且有力地实现，但它往往对某些参数变量敏感。这些变量包括消退和复吸测试环节的安排、足击应激的强度和持续时间，以及在消退和复吸测试期间与药物相关线索的存在情况。在这里，我们介绍一种用于足击诱导可卡因寻求行为恢复的方案，我们一直成功地使用该方案来研究应激与可卡因寻求行为之间的关系。
