Graduate Center, City University of New York, New York, NY 10016, USA.
Psychopharmacology (Berl). 2013 Aug;228(4):651-8. doi: 10.1007/s00213-013-3069-x. Epub 2013 Apr 18.
Most animal research on drug relapse involves the reinstatement model where abstinence is a result of drug removal (extinction). However, abstinence in humans often results from the aversive consequences that accompany drug seeking (conflict situation). This study was aimed at using a conflict-based animal model of abstinence/relapse in rats self-administering heroin or cocaine.
Rats were trained to self-administer heroin (0.05 mg kg(-1) injection(-1)) or cocaine (0.5 mg kg(-1) injection(-1)) with each injection paired with a light cue. After stable responding was demonstrated, the floor near the levers was electrified, creating a barrier, in order to model the negative consequences of continued drug seeking. Shock intensities were increased over sessions until no responses occurred for three consecutive sessions. During a relapse test, where shock was maintained,the capacity of noncontingent drug cue presentations to induce active lever pressing was assessed.
Ten of ten heroin animals and three of eight cocaine animals exposed to noncontingent cue presentations resumed responding. During the relapse test, for both drug groups, active lever pressing was significantly higher than during abstinence but only in the heroin group was it significantly higher than inactive lever pressing.
The implementation of negative consequences for drug seeking can result in its cessation just as they might in human addicts. Similarly, exposure to drug cues can lead to resumption of drug seeking. This model may be useful for studying the mechanisms underlying abstinence and relapse and for developing strategies to prevent relapse.
大多数关于药物复吸的动物研究都涉及到重新给药模型,在该模型中,戒断是药物去除(消退)的结果。然而,人类的戒断通常是由于药物寻求(冲突情境)带来的不良后果。本研究旨在使用基于冲突的大鼠海洛因或可卡因自我给药的戒断/复吸动物模型。
大鼠接受训练,以自我注射海洛因(0.05mg/kg 注射-1)或可卡因(0.5mg/kg 注射-1),每次注射与光提示配对。在稳定的反应出现后,靠近杠杆的地板被通电,形成一个障碍,以模拟持续药物寻求的负面后果。随着时间的推移,电击强度增加,直到连续三个疗程没有反应。在复吸测试中,维持电击的情况下,评估非偶联药物线索呈现对主动杠杆按压的诱导作用。
在非偶联线索呈现下,10 只海洛因动物中的 10 只和 8 只可卡因动物中的 3 只恢复了反应。在复吸测试中,对于这两个药物组,主动杠杆按压显著高于戒断期,但只有海洛因组的主动杠杆按压显著高于非活跃杠杆按压。
对药物寻求的负面后果的实施可以导致其停止,就像在人类成瘾者中一样。同样,暴露于药物线索会导致药物寻求的恢复。这种模型可能有助于研究戒断和复吸的机制,并开发预防复吸的策略。