Contextual memory plays an important role in development and maintenance of drug addiction. However, little is known about of the role contextual memory in the emergence of a negative emotional state in the withdrawal period. Therefore, this study investigated anxiety-like behavior in acute and protracted morphine withdrawal of mice submitted to a locomotor sensitization protocol and the influence of contextual memory on this behavior. Male adult C57Bl6 mice were subjected to morphine locomotor sensitization and anxiety-like behavior was assessed by using the elevated plus maze test (EPM). To evaluate associative memory, the mice were re-exposed to the context of locomotor sensitization immediately before EPM. As expected, repeated morphine administrations promoted locomotor sensitization, seen as a gradual increase in the distance traveled during the acquisition phase. There was an increase in anxiety-like behavior upon acute withdrawal, as indicated by a decrease in open arms activity (OAA), but this effect dissipated over time. However, when the context was presented, mice in protracted withdrawal showed enhanced anxiety-like behavior, indicated by an increase in closed arms activity (CAA). This effect was context specific since re-exposure in an alternative context did not change the anxiety-like behavior. Treatment with diazepam counteracted the decrease in OAA in acute withdrawal and the increase in CAA induced by context re- exposure during protracted abstinence. Thus, repeated morphine administration induced a negative emotional state when the drug was discontinued. The context associated with drug exposure played a pivotal role in the appearance of anxiety-like behavior, even long after drug discontinuation. There were differences in the patterns of anxiety behaviors in acute (unconditioned anxiety-like behavior) and protracted (conditioned anxiety-like behavior) withdrawal since the former was characterized by a passive behavioral strategy and the latter by an active behavioral strategy.

语境记忆在药物成瘾的发展和维持中起着重要作用。然而，人们对于在退缩期出现负面情绪状态时背景记忆的作用知之甚少。因此，本研究调查了接受运动敏化方案的小鼠在急性和长期吗啡戒断中的焦虑样行为，以及情境记忆对该行为的影响。对雄性成年C57B16小鼠进行吗啡运动致敏，并通过高架迷宫测试（EPM）评估焦虑样行为。为了评估联想记忆，将小鼠在EPM之前立即再次暴露于运动致敏的环境中。如预期的那样，反复服用吗啡可促进运动敏化，被视为获取阶段中行进距离的逐渐增加。急性停药后焦虑样行为有所增加，如张开双臂活动（OAA）减少所表明，但这种影响会随着时间的流逝而消失。但是，当出现这种情况时，长时间停药的小鼠表现出增强的焦虑样行为，这表现为闭合臂活动（CAA）的增加。这种效果是特定于情境的，因为在替代情境中再次暴露并不会改变焦虑样行为。用地西epa治疗可抵消长期戒酒期间急性戒断时OAA的降低和因环境再暴露引起的CAA的升高。因此，停药后重复服用吗啡会导致情绪低落。即使在停药后很长时间，与药物暴露相关的环境在焦虑样行为的出现中也起着关键作用。急性（无条件的焦虑样行为）和长期（有条件的焦虑样行为）戒断的焦虑行为模式存在差异，因为前者的特点是被动的行为策略，后者的特点是主动的行为策略。