The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats
The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats
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DOI：
10.1038/sj.npp.1300653
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发表时间：
2005-05-01
影响因子：
7.6
通讯作者：
Ferris, CF
中科院分区：
文献类型：
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作者：
Febo, M;Segarra, AC;Ferris, CF
在可卡因成瘾的动物模型中使用功能性磁共振成像（fMRI）是研究导致这种精神疾病的神经适应的宝贵工具。我们在清醒大鼠中使用血氧水平依赖（BOLD）MRI来识别受重复可卡因给药影响的神经元回路。给大鼠注射可卡因（15 mg/kg，i. p.）或其赋形剂7天，戒断注射1周，并在功能成像期间用脑室内可卡因注射激发。急性可卡因在众所周知的富含单胺的大脑区域，如前额叶皮层、背侧纹状体、感觉皮层、海马、丘脑和中脑区域产生了强烈的阳性BOLD反应。然而，重复可卡因给药导致较低的BOLD反应，在前额皮质，无颗粒岛叶皮质，丘脑核，腹侧苍白球，丘脑背内侧，以及其他大脑区域。BOLD强度的降低与未用药大鼠和重复暴露于可卡因的大鼠之间的脑血管反应性变化无关，因此，对可卡因反应的较低代谢活化可能反映了重复给药后神经元和/或突触活性的降低。
The use of functional magnetic resonance imaging (fMRI) in animal models of cocaine addiction is an invaluable tool for investigating the neuroadaptations that lead to this psychiatric disorder. We used blood-oxygen-level-dependent (BOLD) MRI in awake rats to identify the neuronal circuits affected by repeated cocaine administration. Rats were given an injection of cocaine (15 mg/kg, i.p.) or its vehicle for 7 days, abstained from injections for 1 week, and challenged with an intracerebroventricular cocaine injection during functional imaging. Acute cocaine produced robust positive BOLD responses across well-known monoamine-enriched brain regions, such as the prefrontal cortex, nucleus accumbens, dorsal striatum, sensory cortex, hippocampus, thalamus, and midbrain areas. However, repeated cocaine administration resulted in lower BOLD responses in the prefrontal cortex, agranular insular cortex, nucleus accumbens, ventral pallidum, and dorsomedial thalamus, among other brain regions. Reductions in BOLD intensity were not associated with variations in cerebrovascular reactivity between drug naive rats and those repeatedly exposed to cocaine, Therefore, the lower metabolic activation in response to cocaine could reflect a reduced neuronal and/or synaptic activity upon repeated administration.