Li Yingying, Zheng Xigeng, Xu Na, Zhang Yue, Liu Zhengkui, Bai Yunjing
CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Psychopharmacology (Berl). 2017 Apr;234(8):1277-1292. doi: 10.1007/s00213-017-4565-1. Epub 2017 Feb 22.
The negative affective state, e.g., anhedonia, emerges after abstinence from abused drugs may be linked to the motivational processes of drug craving and relapse. Although anhedonia diminishes over time with drug abstinence, it is not yet rather explicit whether anhedonia exists or not following protracted withdrawal.
The behavioral responses to natural rewards were examined after 2 to 3 weeks withdrawal from morphine. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. The consummatory and motivational behaviors for three natural rewards (sucrose solutions 4, 15, and 60%, social stimulus: male rat, and sexual stimulus: estrous female rat) were examined under varied testing conditions.
The morphine-withdrawn rats significantly increased their intake of 15% sucrose solution during the 1-h consumption test and their operant responding for 15% sucrose solution under a progressive ratio (PR) schedule of reinforcement. When obtaining a reinforcer was associated with a 0.5 mA foot shock under a PR-punishment schedule, the morphine-withdrawn rats showed a higher performance for 60% sucrose solution. Meanwhile, the morphine-withdrawn rats displayed a higher motivation to sexual stimulus during the free-approach test and more approaching behaviors towards sexual stimulus in a conflict-based approach test (concurrent presence of reward and aversive stimulus).
No anhedonia-like behavior but sensitized behaviors for natural rewards were found after long-term morphine withdrawal. Notably, the morphine-withdrawn rats displayed persistent motivated behaviors for high-value rewards (60% sucrose and sexual stimulus) in the conflict tests suggesting impairments in inhibitory control in morphine-treated rats.
消极情感状态，如快感缺失，在停止滥用药物后出现，可能与药物渴望和复发的动机过程有关。尽管随着药物戒断，快感缺失会随时间减少，但在长期戒断后是否存在快感缺失尚不明确。
在从吗啡戒断2至3周后，检查对自然奖励的行为反应。雄性大鼠预先接受5天的类似暴饮暴食的吗啡范式或每日生理盐水注射。在不同的测试条件下，检查对三种自然奖励（4%、15%和60%的蔗糖溶液、社会刺激：雄性大鼠、性刺激：发情期雌性大鼠）的消费和动机行为。
在1小时的消费测试中，吗啡戒断大鼠显著增加了对15%蔗糖溶液的摄入量，并且在渐进比率（PR）强化程序下对15%蔗糖溶液的操作性反应增加。当在PR惩罚程序下获得强化物与0.5毫安的足部电击相关联时，吗啡戒断大鼠对60%蔗糖溶液表现出更高的表现。同时，在自由接近测试中，吗啡戒断大鼠对性刺激表现出更高的动机，并且在基于冲突的接近测试（奖励和厌恶刺激同时存在）中对性刺激表现出更多的接近行为。
长期吗啡戒断后未发现类似快感缺失的行为，但对自然奖励的行为敏感。值得注意的是，吗啡戒断大鼠在冲突测试中对高价值奖励（60%蔗糖和性刺激）表现出持续的动机行为，这表明吗啡处理的大鼠在抑制控制方面存在损伤。
