Gracy K N, Dankiewicz L A, Weiss F, Koob G F
Division of Psychopharmacology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pharmacol Biochem Behav. 2000 Mar;65(3):489-94. doi: 10.1016/s0091-3057(99)00234-8.
The clinical literature suggests that exposure to environmental stimuli previously associated with heroin availability may precipitate relapse. However, experimental studies elucidating the significance of learned associations between drug availability and reinstatement of heroin-seeking behavior in the rat are still scarce. To examine the role of environmental stimuli in reinstatement of heroin-seeking behavior, rats were trained to associate discriminative stimuli (DS+) with intravenous heroin availability vs. nonreward [i.e., availability of intravenous saline (DS-)]. The animals then were subjected to extinction training during which the discriminative stimuli were not presented, and lever pressing did not result in drug or saline infusion. The resistance to extinction varied greatly among animals (2.5-11.4 weeks). When the discriminative stimuli were reintroduced, the DS+ reinstated responding while the DS- did not. The average number of responses for heroin during the reinstatement trial (12.8) paralleled the average responding for heroin during discrimination training (12.6), suggesting that the associations between environmental stimuli and drug availability are long-lasting and powerful motivators of drug-seeking behavior.
临床文献表明，暴露于先前与海洛因可得性相关的环境刺激可能会引发复吸。然而，阐明在大鼠中药物可得性与海洛因寻求行为恢复之间习得关联的重要性的实验研究仍然很少。为了研究环境刺激在海洛因寻求行为恢复中的作用，训练大鼠将辨别性刺激（DS+）与静脉注射海洛因可得性与无奖励情况（即静脉注射生理盐水可得性，DS-）联系起来。然后对动物进行消退训练，在此期间不呈现辨别性刺激，按压杠杆也不会导致药物或生理盐水注入。动物之间的消退抵抗差异很大（2.5 - 11.4周）。当重新引入辨别性刺激时，DS+恢复了反应，而DS-则没有。恢复试验期间对海洛因的平均反应次数（12.8）与辨别训练期间对海洛因的平均反应次数（12.6）相似，这表明环境刺激与药物可得性之间的关联是持久且强大的药物寻求行为动机。
