Department of Psychiatry, Chonbuk National University Medical School and Institute for Medical Sciences, San 2-20 Geumam-dong, Deokjin-gu, Jeonju 561-756, South Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 16;34(6):1054-9. doi: 10.1016/j.pnpbp.2010.05.024.
As adolescence is a critical period when dopaminergic neuronal maturation peaks, we hypothesized that 6-hydroxydopamine (OHDA) lesions of the medial prefrontal cortex (mPFC) in adolescent rats would have more negative effects than lesions in adult rats. Therefore, we investigated the effects of 6-OHDA lesions of the mPFC in adolescent and adult rats on stress-induced c-fos expression in the brain. Adolescent and adult Sprague-Dawley rats, aged 4 and 7 weeks on arrival, respectively, were studied. 6-OHDA (8.0 microg) for the lesion groups and ascorbic acid for the sham groups were injected bilaterally into the mPFC. All animals were pretreated with desipramine 30 min before being anesthetized. The control group did not undergo any surgery-related procedure except the desipramine injection. After recovery for 1 week, the rats were subjected to restraint stress for 1 h. Immediately after the stress, the rats were killed and c-fos immunohistochemistry was examined. The c-fos expression in the nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), CA1, CA3, dentate gyrus (DG), central amygdaloid (Ce), basolateral amygdaloid (BL), and temporal cortex (Tc) was compared. Adolescent rats with 6-OHDA lesions subjected to restraint stress had greater c-fos expression in the AcbC, AcbSh, DG, Ce, BL, and Tc, compared to the sham and control groups, whereas these differences were not observed among the adult groups. These results suggest that a hypodopaminergic state in the mPFC of adolescent rats, but not adult rats, is related to increased sensitivity to stress, suggesting that damage to or maldevelopment of dopaminergic neurons during adolescence has an age-specific effect. Further research is warranted to investigate the mechanism of the age-specific effect of 6-OHDA lesions of the mPFC.
青春期是多巴胺能神经元成熟的关键时期，我们假设，在青春期大鼠的内侧前额叶皮质（mPFC）中进行 6-羟多巴胺（OHDA）损伤，会比在成年大鼠中进行损伤产生更负面的影响。因此，我们研究了在青春期和成年大鼠中，mPFC 的 6-OHDA 损伤对大脑应激诱导的 c-fos 表达的影响。到达时分别为 4 周和 7 周龄的青春期和成年 Sprague-Dawley 大鼠被用于研究。损伤组的双侧 mPFC 注射 6-OHDA（8.0 μg），假手术组注射抗坏血酸。所有动物在麻醉前 30 分钟预先给予去甲丙咪嗪。对照组除了去甲丙咪嗪注射外，没有进行任何与手术相关的程序。恢复 1 周后，大鼠进行 1 小时的束缚应激。应激结束后立即处死大鼠，并进行 c-fos 免疫组织化学检查。比较核壳（AcbC）、核壳（AcbSh）、CA1、CA3、齿状回（DG）、中央杏仁核（Ce）、基底外侧杏仁核（BL）和颞叶皮层（Tc）中的 c-fos 表达。与假手术和对照组相比，经受束缚应激的青春期 6-OHDA 损伤大鼠的 AcbC、AcbSh、DG、Ce、BL 和 Tc 中的 c-fos 表达增加，而成年组之间则没有观察到这些差异。这些结果表明，青春期大鼠 mPFC 中的低多巴胺状态与对压力的敏感性增加有关，但成年大鼠则不然，这表明多巴胺能神经元在青春期的损伤或发育不良与年龄特异性效应有关。需要进一步研究来探讨 mPFC 的 6-OHDA 损伤的年龄特异性效应的机制。
