Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Neuropsychopharmacology. 2023 Jan;48(2):290-298. doi: 10.1038/s41386-021-01136-w. Epub 2021 Aug 12.
Previous studies in humans and in animals have shown dramatic effects of cocaine on measures of brain function that persist into abstinence. The purpose of this study was to examine the neurobiological consequences of abstinence from cocaine, using a model that removes the potential confound of cocaine cues. Adult male rhesus monkeys self-administered cocaine (0.3 mg/kg/injection; N = 8) during daily sessions or served as food-reinforcement controls (N = 4). Two times per week, monkeys were placed in a neutral environment and presented with a cartoon video for ~30 min, sometimes pre- and sometimes post-operant session, but no reinforcement was presented during the video. After ~100 sessions and when the cocaine groups had self-administered 900 mg/kg cocaine, the final experimental condition was a terminal 2-[C]-deoxyglucose procedure, which occurred in the neutral (cartoon video) environment; for half of the monkeys in each group, this occurred after 1 day of abstinence and for the others after 30 days of abstinence. Rates of local cerebral glucose metabolism were measured in 57 brain regions. Global rates of cerebral metabolism were significantly lower in animals 1 day and 30 days post-cocaine self-administration when compared to those of food-reinforced controls. Effects were larger in 30- vs. 1-day cocaine abstinence, especially in prefrontal, parietal and cingulate cortex, as well as dorsal striatum and thalamus. Because these measures were obtained from monkeys while in a neutral environment, the deficits in glucose utilization can be attributed to the consequences of cocaine exposure and not to effects of conditioned stimuli associated with cocaine.
先前的人体和动物研究表明，可卡因对大脑功能的测量有显著影响，这些影响在戒断后仍持续存在。本研究的目的是使用一种去除可卡因线索潜在混杂因素的模型，来研究可卡因戒断的神经生物学后果。成年雄性恒河猴在每日的实验中自我注射可卡因（0.3mg/kg/次；N=8），或作为食物强化对照组（N=4）。每周两次，猴子被放置在一个中性环境中，并观看一个卡通视频约 30 分钟，有时在操作前，有时在操作后，但在观看视频期间没有呈现强化物。经过约 100 次实验后，当可卡因组自我注射了 900mg/kg 的可卡因后，最后一个实验条件是 2-[C]-脱氧葡萄糖程序，这个程序在中性（卡通视频）环境中进行；对于每组中的一半猴子，这个程序在可卡因戒断 1 天后进行，而对于另一半猴子则在可卡因戒断 30 天后进行。测量了 57 个脑区的局部脑葡萄糖代谢率。与食物强化对照组相比，自我注射可卡因后 1 天和 30 天的动物的大脑整体代谢率显著降低。与可卡因戒断 1 天相比，可卡因戒断 30 天的影响更大，特别是在前额皮质、顶叶和扣带回皮质以及背侧纹状体和丘脑。由于这些测量是在猴子处于中性环境时获得的，因此葡萄糖利用率的缺陷可以归因于可卡因暴露的后果，而不是与可卡因相关的条件刺激的影响。
