Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA.
Psychopharmacology (Berl). 2014 Oct;231(21):4211-8. doi: 10.1007/s00213-014-3560-z. Epub 2014 Apr 15.
Differences in brain function in cocaine users can occur even when frank deficits are not apparent, indicating neuroadaptive consequences of use. Using monkeys to investigate altered metabolic activity following chronic cocaine self-administration allows an assessment of altered function due to cocaine use, without confounding pre-existing differences or polysubstance use often present in clinical studies.
To evaluate alterations in metabolic function during a working memory task in the prefrontal cortex and the cerebellum following 1 year of chronic cocaine self-administration followed by a 20 month drug-free period.
Fluorodeoxyglucose ((18)F) PET imaging was used to evaluate changes in relative regional metabolic activity associated with a delayed match to sample working memory task. Chronic cocaine animals were compared to a control group, and region of interest analyses focused on the dorsolateral prefrontal cortex (DLPFC) and cerebellum.
Despite no differences in task performance, in the cocaine group, the cerebellum showed greater metabolic activity during the working memory task (relative to the control task) compared to the control group. There was also a trend toward a significant difference between the groups in DLPFC activity (p = 0.054), with the cocaine group exhibiting lower DLPFC metabolic activity during the delay task (relative to the control task) than the control group.
The results support clinical indications of increased cerebellar activity associated with chronic cocaine exposure. Consistent with evidence of functional interactions between cerebellum and prefrontal cortex, these changes may serve to compensate for potential impairments in functionality of DLPFC.
即使在没有明显缺陷的情况下，可卡因使用者的大脑功能也可能存在差异，这表明使用可卡因会导致神经适应性改变。使用猴子来研究慢性可卡因自我给药后代谢活性的改变，可以评估由于可卡因使用而导致的功能改变，而不会受到临床研究中经常存在的预先存在的差异或多种物质使用的混杂。
在慢性可卡因自我给药 1 年后和 20 个月的无毒品期后，评估前额叶皮层和小脑在执行工作记忆任务时代谢功能的改变。
使用氟脱氧葡萄糖 ((18)F) PET 成像来评估与延迟匹配样本工作记忆任务相关的相对区域代谢活性的变化。将慢性可卡因动物与对照组进行比较，并进行感兴趣区域分析，重点关注背外侧前额叶皮层 (DLPFC) 和小脑。
尽管在任务表现上没有差异，但在可卡因组中，小脑在工作记忆任务期间（相对于对照任务）表现出比对照组更高的代谢活性。DLPFC 活动组间也存在显著差异的趋势（p=0.054），可卡因组在延迟任务期间（相对于对照任务）的 DLPFC 代谢活性低于对照组。
这些结果支持了慢性可卡因暴露与小脑活动增加相关的临床证据。与小脑和前额叶皮层之间存在功能相互作用的证据一致，这些变化可能有助于补偿 DLPFC 功能的潜在损害。
