Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Medical Discovery Team On Addiction, University of Minnesota, Minneapolis, MN, USA.
Psychopharmacology (Berl). 2023 Mar;240(3):461-476. doi: 10.1007/s00213-022-06218-1. Epub 2022 Sep 7.
Addiction is characterized by intermittent drug seeking despite rising costs. This behavior is heavily influenced by environmental stimuli that signal drug availability and reinforce drug seeking.
To establish the relationship between three key aspects of human drug use in rats: the intermittent, binge nature of drug intake, the motivational conflict of drug seeking in the face of escalating negative costs, and the ability of different drug cues to interact to modulate relapse.
Male and female rats were trained to self-administer cocaine on an intermittent access schedule, where brief drug-availability states were signaled by a shift in the ambient lighting of the environment, and cocaine infusions were signaled by a separate proximal discrete cue. Rats then went through a conflict procedure, where foot shock intensity associated with cocaine seeking was escalated until intake was suppressed. We then completed relapse tests where the drug-delivery cue was noncontingently presented alone, or in the context of dynamic drug-availability state transitions.
Intermittent access spurred psychomotor sensitization and binge-like cocaine intake. The intensity of binge-like drug taking during training was predictive of later drug seeking despite escalating costs during conflict. In relapse tests, the ability of a proximal discrete drug cue to trigger relapse was gated by the presence of a global cue signaling drug-availability state transitions.
Our results suggest that the pattern of drug intake plays a role in many features of addiction, including modifying an individual's willingness to endure high costs associated with drug seeking. Furthermore, our studies indicate that drug-related sensory information can be hierarchically organized to exert a dynamic modulating influence on drug-seeking motivation.
成瘾的特征是尽管成本不断上升，但仍会间歇性地寻求药物。这种行为受到环境刺激的强烈影响，这些刺激信号药物的可用性并加强药物寻求。
在大鼠的人类药物使用的三个关键方面建立关系：药物摄入的间歇性、 binge 性质，在不断增加的负面成本面前寻求药物的动机冲突，以及不同药物线索相互作用调节复发的能力。
雄性和雌性大鼠被训练在间歇性访问计划中自行服用可卡因，其中环境照明的变化标志着短暂的药物可用性状态，而可卡因输注则由单独的近端离散线索标志。然后，大鼠经历了一个冲突程序，其中与可卡因寻求相关的足部电击强度逐渐增加，直到摄入被抑制。然后，我们完成了复发测试，其中药物输送线索非条件地单独呈现，或在动态药物可用性状态转换的背景下呈现。
间歇性访问刺激了精神运动敏化和 binge 样可卡因摄入。训练期间 binge 样药物摄入的强度预测了冲突期间成本不断上升后药物寻求的后续。在复发测试中，近端离散药物线索触发复发的能力受到全球线索信号药物可用性状态转换的调节。
我们的结果表明，药物摄入模式在成瘾的许多特征中起作用，包括改变个体对与药物寻求相关的高成本的意愿。此外，我们的研究表明，与药物相关的感觉信息可以被分层组织，对药物寻求动机产生动态调节影响。
