Department of Psychology, University of Kentucky, 741 S. Limestone, 448C BBSRB, Lexington, KY 40536-0509, USA.
Psychopharmacology (Berl). 2012 Jul;222(2):257-67. doi: 10.1007/s00213-012-2641-0. Epub 2012 Jan 17.
Understanding the neurobehavioral mechanisms underlying dysregulated cocaine intake is important for the development of new cocaine abuse therapies.
The current study determined if cocaine escalation under extended access conditions (6-h access) is regulated by discrimination learning processes.
Rats were initially trained on cocaine self-administration (0.1 or 0.25 mg/kg/infusion) using a fixed ratio 1 (FR 1) schedule under 1-h access for 12 sessions. Some rats were then trained to self-administer cocaine under 1-h or 6-h access conditions exclusively for 14 additional sessions, while other rats were trained under both 1- and 6-h access conditions that were cued or noncued for 28 additional sessions (14 sessions for each 1- and 6-h access). Two additional groups of rats were initially trained to self-administer cocaine using an FR 1 schedule under 10-min access for 12 sessions; half of the animals were then switched to 60-min access conditions for 14 additional sessions.
When access conditions were differentially cued, escalation of cocaine intake was evident in animals with both 1- and 6-h access conditions during the escalation phase. Escalation also was evident in animals initially trained with 10-min access and then switched to 60-min access.
The results demonstrate that dysregulated and regulated intakes can be expressed within the same animal, indicating that escalation is context-dependent. Furthermore, escalated cocaine intake can be expressed under 1-h access conditions. Overall, these results suggest that escalated cocaine intake may be representative of discrimination-dependent regulated intake rather than addiction-like, compulsive intake.
理解可卡因摄入失调的神经行为机制对于开发新的可卡因滥用治疗方法很重要。
本研究旨在确定在延长的获取条件（6 小时获取）下可卡因的增加是否受辨别学习过程的调节。
最初，通过使用 1 小时获取条件进行 12 个疗程，对大鼠进行可卡因自我给药（0.1 或 0.25mg/kg/次）的训练，采用固定比率 1（FR1）时间表。然后，一些大鼠被训练在 1 小时或 6 小时获取条件下仅进行 14 个额外疗程的自我给药，而其他大鼠则在 1 小时和 6 小时获取条件下进行训练，这些条件是有提示或无提示的，共进行 28 个额外疗程（每个 1 小时和 6 小时获取条件各 14 个疗程）。另外两组大鼠最初被训练在 10 分钟获取条件下使用 FR1 时间表进行 12 个疗程的自我给药；然后，其中一半动物被切换到 60 分钟获取条件进行 14 个额外疗程。
当获取条件存在差异提示时，在增加阶段，具有 1 小时和 6 小时获取条件的动物可卡因摄入量明显增加。最初在 10 分钟获取条件下接受训练然后切换到 60 分钟获取条件的动物也表现出可卡因摄入量增加。
结果表明，失调和调节的摄入量可以在同一动物中表现出来，这表明增加是依赖于环境的。此外，1 小时获取条件下可表现出可卡因摄入量增加。总体而言，这些结果表明，可卡因的增加摄入量可能代表依赖于辨别调节的摄入，而不是类似于成瘾的强迫性摄入。
