Laboratorio de Neuroepigenética, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, and Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, CONICET, C1428EGA, Buenos Aires, Argentina.
Psychopharmacology (Berl). 2019 Dec;236(12):3525-3539. doi: 10.1007/s00213-019-05321-0. Epub 2019 Jul 6.
Cocaine base paste (CBP) is an illegal drug of abuse usually consumed by adolescents in a socio-economically vulnerable situation. Repeated drug use targets key brain circuits disrupting the processes that underlie emotions and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate-early genes (IEGs). Nevertheless, changes in transcriptional regulation associated with CBP consumption remain unknown.
We aimed to describe behavioral phenotype related to locomotion, anxiety-like behavior, and memory of CBP-injected mice and to study IEGs expression after an abstinence period.
Five-week-old female CF-1 mice were i.p. injected daily with vehicle or CBP (40 mg/kg) for 10 days and subjected to a 10-day period of abstinence. Open field and novel object recognition tests were used to evaluate locomotion and anxiety-like behaviors and recognition memory, respectively, during chronic administration and after abstinence. After abstinence, prefrontal cortex (mPFC) and nucleus accumbens (NAc) were isolated and gene expression analysis performed through real-time PCR.
We found an increase in locomotion and anxiety-like behavior during CBP administration and after the abstinence period. Furthermore, the CBP group showed impaired recognition memory after abstinence. Egr1, FosB, ΔFosB, Arc, Bdnf, and TrkB expression was upregulated in CBP-injected mice in NAc and FosB, ΔFosB, Arc, and Npas4 expression was downregulated in mPFC. We generated an anxiety score and found positive and negative correlations with IEGs expression in NAc and mPFC, respectively.
Our results suggest that chronic CBP exposure induced alterations in anxiety-like behavior and recognition memory. These changes were accompanied by altered IEGs expression.
可卡因碱（CBP）是一种非法滥用药物，通常被社会经济弱势青少年吸食。反复使用毒品会靶向关键的大脑回路，扰乱情绪和认知的基础过程。这种神经适应的基础是即时早期基因（IEGs）表达的变化。然而，与 CBP 消费相关的转录调节变化仍不清楚。
我们旨在描述与运动、焦虑样行为和 CBP 注射小鼠记忆相关的行为表型，并研究戒断期后 IEGs 的表达。
5 周龄雌性 CF-1 小鼠每天腹腔注射载体或 CBP（40mg/kg），共 10 天，并进行 10 天的戒断期。在慢性给药和戒断后，使用旷场和新物体识别测试分别评估运动和焦虑样行为以及识别记忆。戒断后，分离前额叶皮层（mPFC）和伏隔核（NAc），并通过实时 PCR 进行基因表达分析。
我们发现 CBP 给药期间和戒断后运动和焦虑样行为增加。此外，CBP 组在戒断后表现出识别记忆受损。CBP 注射小鼠的 NAc 中 Egr1、FosB、ΔFosB、Arc、Bdnf 和 TrkB 表达上调，mPFC 中 FosB、ΔFosB、Arc 和 Npas4 表达下调。我们生成了一个焦虑评分，并发现与 NAc 和 mPFC 中的 IEGs 表达呈正相关和负相关。
我们的结果表明，慢性 CBP 暴露会导致焦虑样行为和识别记忆改变。这些变化伴随着 IEGs 表达的改变。
