State Key Laboratory of Brain and Cognitive Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China.
Brain Res. 2010 Jan 22;1311:86-92. doi: 10.1016/j.brainres.2009.11.049. Epub 2009 Nov 27.
Drug addiction is increasingly viewed as the expression of abnormal associative learning following repeated exposures to the drugs of abuse. Previous studies have demonstrated that the patterns of repetition such as frequency and spacing are important to many kinds of learning and memory retention. We hypothesized that drug repetition pattern might affect the reward-related learning although the total doses of the drug were the same. In the present study, we tested morphine-induced place preference following either regular or irregular pattern of morphine pairing in rats. Regular morphine group received morphine administration daily at a regular time with the same dose. Irregular morphine groups received morphine administration either at the same time but irregular doses, irregular time but same dose, or irregular time and irregular doses. We found that rats, who received irregular morphine pairing, exhibited similar acquisition of place preference but different preference retentions compared with regular morphine-treated rats after the same total dose of morphine. Rats, who received morphine administration at the same time but irregular doses and at irregular time and irregular doses, showed rapid disruption of place preference than the regular morphine group. Rats, who received morphine at irregular time but the same dose, showed similar retention of place preference to regular morphine group. Our results suggest that the pattern of drug pairing plays an important role in the retention of reward-related memory. This study may provide new evidence to broaden our understanding of the development and maintenance of drug craving.
药物成瘾越来越被视为在反复暴露于滥用药物后异常联想学习的表现。先前的研究表明，重复的模式，如频率和间隔，对许多种类的学习和记忆保留都很重要。我们假设，尽管药物的总剂量相同，但药物重复模式可能会影响与奖励相关的学习。在本研究中，我们测试了在大鼠中给予规律或不规则吗啡配对模式后的吗啡诱导的位置偏好。常规吗啡组每天在固定时间给予相同剂量的吗啡。不规则吗啡组要么在相同时间给予不同剂量的吗啡，要么在相同剂量但不同时间给予吗啡，要么在不同时间给予不同剂量的吗啡。我们发现，与接受常规吗啡治疗的大鼠相比，接受不规则吗啡配对的大鼠在接受相同总剂量的吗啡后，表现出相似的位置偏好获得，但偏好保留不同。与常规吗啡组相比，同时给予不规则剂量和不规则时间及不规则剂量的大鼠，表现出更快的位置偏好破坏。给予相同剂量但不规则时间的吗啡的大鼠，其位置偏好的保留与常规吗啡组相似。我们的结果表明，药物配对模式在与奖励相关的记忆保留中起着重要作用。这项研究可能为拓宽我们对药物渴望的发展和维持的理解提供新的证据。
