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Residual deficits in functional brain activity after chronic cocaine self-administration in rhesus monkeys
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2021-08-12 , DOI: 10.1038/s41386-021-01136-w
Linda J Porrino 1 , Hilary R Smith 1 , Thomas J R Beveridge 1 , Mack D Miller 1 , Susan H Nader 1 , Michael A Nader 1
Affiliation  

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-[14C]-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.



中文翻译:


恒河猴长期自我服用可卡因后大脑功能活动残留缺陷



先前对人类和动物的研究表明,可卡因对大脑功能的影响会持续到戒毒后。本研究的目的是使用消除可卡因线索潜在混淆的模型来检查戒除可卡因的神经生物学后果。成年雄性恒河猴在每日训练期间自行注射可卡因(0.3 毫克/公斤/注射; N = 8)或作为食物强化对照( N = 4)。每周两次,猴子被放置在中性环境中,并播放约 30 分钟的卡通视频,有时在手术前,有时在手术后,但视频期间没有提供强化。经过约 100 次疗程后,当可卡因组自行施用 900 mg/kg 可卡因时,最终实验条件是最终 2-[ 14 C]-脱氧葡萄糖程序,该程序发生在中性(卡通视频)环境中;对于每组中的一半猴子,这种情况发生在禁欲 1 天后,而其他猴子则在禁欲 30 天后发生。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,自我施用可卡因后 1 天和 30 天的动物的整体脑代谢率显着降低。与 1 天可卡因戒断相比,30 天戒断效果更大,特别是在前额叶、顶叶和扣带皮层,以及背侧纹状体和丘脑。因为这些测量是在中性环境中从猴子身上获得的,所以葡萄糖利用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。

更新日期:2021-08-13
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