High and escalating levels of cocaine intake are dissociable from subsequent incentive motivation for the drug in rats
High and escalating levels of cocaine intake are dissociable from subsequent incentive motivation for the drug in rats
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DOI：
10.1007/s00213-017-4773-8
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Samaha, Anne-Noel
中科院分区：
文献类型：
--
作者：
Allain, Florence;Bouayad-Gervais, Karim;Samaha, Anne-Noel
人们认为摄入大量且不断增加的可卡因对成瘾的发展是必要的。因此，一种广泛使用的药物自我给药动物模型涉及在长时间的实验阶段（LgA）让动物持续获得药物，因为这会导致摄入量较高且不断上升。然而，人类可卡因成瘾者可能是以间歇而非持续的方式使用该药物，从而使大脑中的可卡因水平出现峰值。
我们在大鼠身上使用一种间歇获取（IntA）可卡因自我给药程序，研究了可卡因摄入量的增加与后来对该药物的激励动机之间的关系，通过在可卡因强化的累进比率程序下的反应来衡量这种激励动机。
首先，在间歇获取模式下，大鼠在实验阶段内和阶段间都会增加其可卡因使用量。然而，这种增加并不能预测后来对该药物的激励动机。其次，在被限制于低水平且无增加的药物摄入量的间歇获取模式大鼠（IntA - Lim）和摄入高水平且不断增加药物的间歇获取模式大鼠中，对可卡因的激励动机是相似的。最后，与在每次自我给药阶段都能持续获得药物的大鼠（LgA大鼠）相比，IntA - Lim大鼠摄入的可卡因要少得多。然而，在强化的累进比率程序下，IntA - Lim大鼠后来对可卡因的反应更强烈。
摄入大量且不断增加的可卡因似乎并非增加对该药物激励动机的必要条件。以间歇方式摄入可卡因——即使是少量——在产生这种与成瘾相关的变化方面更为有效。因此，除了药物摄入量之外，药物使用的时间动力学能够预测药物使用随时间的变化。
Taking high and increasing amounts of cocaine is thought to be necessary for the development of addiction. Consequently, a widely used animal model of drug self-administration involves giving animals continuous drug access during long sessions (LgA), as this produces high and escalating levels of intake. However, human cocaine addicts likely use the drug with an intermittent rather than continuous pattern, producing spiking brain cocaine levels.Using an intermittent-access (IntA) cocaine self-administration procedure in rats, we studied the relationship between escalation of cocaine intake and later incentive motivation for the drug, as measured by responding under a progressive ratio schedule of cocaine reinforcement.First, under IntA, rats escalated their cocaine use both within and between sessions. However, escalation did not predict later incentive motivation for the drug. Second, incentive motivation for cocaine was similar in IntA-rats limited to low- and non-escalating levels of drug intake (IntA-Lim) and in IntA-rats that took high and escalating levels of drug. Finally, IntA-Lim rats took much less cocaine than rats given continuous drug access during each self-administration session (LgA-rats). However, IntA-Lim rats later responded more for cocaine under a progressive ratio schedule of reinforcement.Taking large and escalating quantities of cocaine does not appear necessary to increase incentive motivation for the drug. Taking cocaine in an intermittent pattern-even in small amounts-is more effective in producing this addiction-relevant change. Thus, beyond the amount of drug taken, the temporal kinetics of drug use predict change in drug use over time.