Psychobiology Research Group, Institute of Neuroscience, Newcastle University, Newcastle, UK.
Psychopharmacology (Berl). 2011 Oct;217(4):549-57. doi: 10.1007/s00213-011-2311-7. Epub 2011 May 7.
One of the key targets of psychopharmacology research is to determine the potential sites of action of antidepressants in order to characterise their underlying mechanism of action.
Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), the neuroanatomical target-sites of reboxetine (a selective noradrenaline reuptake inhibitor) and bupropion (an antidepressant with stimulatory effects on dopamine and potentially on noradrenaline) were mapped.
Separate groups of rats were challenged acutely or chronically (daily injections for 14 days) with saline or psychoactive compounds and scanned. Subsequent statistical parametric mapping of the main effects of the drug was performed by identifying changes in the BOLD signal.
Acute reboxetine challenge at a low dose (10 mg/kg i.p.) produced positive BOLD responses specifically in the hypothalamus, whereas a larger dose (30 mg/kg i.p.) produced activations in the hypothalamus, anterior hippocampus and prefrontal cortex. Chronic reboxetine (30 mg/kg i.p.) treatment induced increased BOLD responses in the posterior hippocampus and prefrontal cortex, while no significant contrast changes were observed in the hypothalamus and a significant decrease was apparent in the amygdala. In contrast, acute bupropion (15 and 30 mg/kg i.p.) challenge in both doses produced no significant contrast changes in the regions of interest. However, chronic bupropion treatment (30 mg/kg i.p.) produced robust increases in BOLD responses in the hippocampus, amygdala and prefrontal cortex.
In summary, this study demonstrates that reboxetine and bupropion evoke a significant increase in BOLD functional activity in specific regions of the brain, including the hypothalamus, hippocampus, prefrontal cortex and amygdala. Furthermore, the study illustrates the potential value of pharmacological MRI in rodents to delineate pharmacologically induced changes in regional brain function.
精神药理学研究的一个关键目标是确定抗抑郁药的潜在作用部位，以确定其作用机制。
使用血氧水平依赖（BOLD）药理学磁共振成像（phMRI），描绘瑞波西汀（一种选择性去甲肾上腺素再摄取抑制剂）和安非他酮（一种具有刺激多巴胺作用并可能具有刺激去甲肾上腺素作用的抗抑郁药）的神经解剖靶位。
分别用盐水或精神活性化合物急性或慢性（每日注射 14 天）处理大鼠，并进行扫描。通过识别 BOLD 信号的变化，对药物的主要作用进行随后的统计参数映射。
低剂量（10mg/kg i.p.）的瑞波西汀急性挑战会特异性地在前丘脑产生正 BOLD 反应，而较大剂量（30mg/kg i.p.）会在前丘脑、前海马和前额叶皮层产生激活。慢性瑞波西汀（30mg/kg i.p.）治疗会导致后海马和前额叶皮层的 BOLD 反应增加，而下丘脑和杏仁核没有观察到明显的对比变化，且杏仁核的信号明显减少。相比之下，急性安非他酮（15 和 30mg/kg i.p.）挑战在两种剂量下都没有在前脑的感兴趣区域引起明显的对比变化。然而，慢性安非他酮治疗（30mg/kg i.p.）会导致海马体、杏仁核和前额叶皮层的 BOLD 反应显著增加。
总之，这项研究表明，瑞波西汀和安非他酮会引起特定脑区（包括下丘脑、海马体、前额叶皮层和杏仁核）的 BOLD 功能活动显著增加。此外，该研究说明了药理学 MRI 在啮齿动物中描绘区域性脑功能的潜在价值。
