Adhikary Sweta, Caprioli Daniele, Venniro Marco, Kallenberger Paige, Shaham Yavin, Bossert Jennifer M
Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
Addict Biol. 2017 Jul;22(4):977-990. doi: 10.1111/adb.12386. Epub 2016 Mar 14.
In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues.
在经过训练可自行注射甲基苯丙胺的大鼠中，戒断后在与药物相关的情境和离散线索存在时的消退反应会逐渐增加（甲基苯丙胺渴求的潜伏期）。这种潜伏期背后的条件因素尚不清楚。在这里，我们研究了在不同实验条件下甲基苯丙胺渴求的潜伏期，以确定促成这种潜伏期的因素。我们还确定了大鼠对甲基苯丙胺激发的反应在戒断后是否会出现潜伏期。我们训练大鼠在一个独特的情境（情境A）中自行注射甲基苯丙胺14天（每天6小时）。杠杆按压与一个离散的光线索配对。然后，在1天、1周或1个月后，我们在情境A或不同的非药物情境（情境B）中对大鼠组进行测试，观察有无离散线索时的消退反应。随后，我们测试大鼠因接触情境、离散线索或药物激发（0、0.25和0.5mg/kg）而导致的觅药行为恢复情况。在情境A或B的消退实验中，戒断1周和1个月后的操作性反应高于戒断1天后；这种效应与情境无关。与戒断期无关，当反应导致离散线索的偶然递送时，消退实验中的操作性反应更高。消退后，离散线索诱导的觅药行为恢复，但情境或药物激发诱导的觅药行为恢复在戒断后并未逐渐增加。总之，在消退测试中评估的甲基苯丙胺渴求潜伏期主要由非强化操作性反应的时间依赖性增加介导，并且这种效应通过接触离散而非情境线索而增强。
